Showing papers in "International journal of pharmaceutical investigation in 2013"
TL;DR: As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided, these points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking.
Abstract: Recently, fast dissolving films are gaining interest as an alternative of fast dissolving tablets. The films are designed to dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and increased patient compliance. As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided. These points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking. Over-the-counter films for pain management and motion sickness are commercialized in the US markets. Many companies are utilizing transdermal drug delivery technology to develop thin film formats. In the present review, recent advancements regarding fast dissolving buccal film formulation and their evaluation parameters are compiled.
219 citations
TL;DR: The clarity, pH, drug content of all formulations was found to be satisfactory and all the formulations showed sustained drug release for a period of 6 h, which satisfied to treat periodontal disease.
Abstract: Background: The present study was aimed to develop and optimize in situ gel for the treatment of periodontal disease. Materials and Methods: Temperature-sensitive in situ gel containing 0.1% w/v Chlorhexidine hydrochloride was formulated by cold method using different polymers. Preliminary study was carried out to optimize different types and concentration of polymers such as Poloxamer 188, Poloxamer 407, Gellan gum, and Carbopol 934P. Central composite design was employed for optimization of the effect of independent variables such as Poloxamer 407 and Carbopol 934P on responses such as gelation temperature, spreadability, cumulative percentage release at 2 h, and time for 50% drug release (t 50 %). Each formulations were evaluated for clarity, pH, gelation temperature, spreadability, drug content, in vitro drug release, t 50 %, and cumulative percentage drug release at 2 h. Results: Results of evaluation parameters revealed that the drug release, gelation temperature was considerably decreased with increasing t 50 % as the concentration of each polymer was increased. The desirability function was utilized to find out optimized formulation of the factorial design. Formulation F6 showed the highest overall desirability of 0.6283 and, therefore, this formulation was considered to be the optimized formulation. The % relative error was calculated, which showed that observed responses were in close agreement with the predicted values calculated from the generated regression equations. Conclusion: The clarity, pH, drug content of all formulations was found to be satisfactory. Further, all the formulations showed sustained drug release for a period of 6 h, which satisfied to treat periodontal disease.
114 citations
TL;DR: The research performed over the last and current decades on the delivery of various oncolytics for pulmonary delivery for the treatment of lung cancer and inhaled drug delivery devices in cancer therapy are reviewed.
Abstract: Lung cancer is the most malignant cancer today. The treatment of lung cancer continues to be a challenge for oncologists. The direct delivery of chemotherapeutic agents to the lungs could represent a novel therapeutic approach for patients with pulmonary metastases. The large alveolar surface area, the low thickness of the epithelial barrier, and an extensive vascularization make the pulmonary route an ideal route for administration of oncolytics. This paper reviews the research performed over the last and current decades on the delivery of various oncolytics for pulmonary delivery for the treatment of lung cancer. Inhaled drug delivery devices in cancer therapy are also discussed in the present manuscript.
55 citations
TL;DR: This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy.
Abstract: Gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions and genetic disorders. Application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several nonviral and viral gene transfer methods have been developed. Even though the viral agents have a high transferring efficiency, they are difficult to handle due to their toxicity. To overcome the safety problems of the viral counterpart, several nonviral in vitro and in vivo gene delivery systems are developed. Out of these, the most promising and latest systems include polymer-based nonviral gene carriers, dendrimers and physical means like electroporation, microinjection, etc., Shunning of possible immunogenicity and toxicity and the feasibility of repeated administration are some of the merits of nonviral gene delivery systems over viral gene delivery. An ideal nonviral gene carrying system should possess all these merits without any compromise to its gene transferring efficiency. The viral gene delivery systems include lytic and nonlytic vectors for drug delivery. Inspite of its toxicity they are still preferred because of their long term expression, stability and integrity. This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy. Read more...
51 citations
TL;DR: The results indicate that liquid SMEDDS and solid SMED DS of tacrolimus, owing to nano-sized, have potential to enhance the absorption of the drug.
Abstract: Background: Tacrolimus has poor solubility in water ranging from 4 to 12 μ g/mL. The oral bio availabilities of tacrolimus is poor and exhibits high intra and inter-subject variability (4-89%, average 25%) in the liver and the kidney transplant recipients and in patients with renal impairment. Aim: The present study deals with the development and characterization of self-micro-emulsifying drug delivery system to improve the oral bioavailability of poorly soluble drug tacrolimus. Materials and Methods: Solubility of the tacrolimus was estimated in various oils, surfactants, and co-surfactants. Various in vitro tests such as percentage transmittance, emulsification time, cloud point, precipitation, and thermodynamic stabilities were used to find out optimized formulations. Optimized liquid self micro-emulsifying (SMEDDS) were characterized by particle size analysis and converted in solid by using the Florite RE as an adsorbent, which is further characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and particle size analysis. Results: The optimized liquid SMEDDS formulation contained 10% Lauroglycol FCC as an oil, 60% Cremophor RH, and 30% PEG (polyethylene glycol) 400 as a surfactant and co-surfactant respectively. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API (active pharmaceutical ingredient) powder. For optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found 113 nm and 209 nm respectively. The solid state characterization of solid-SMEDDS by SEM, DSC, FTIR, and XRD revealed the absence of crystalline tacrolimus in the solid-SMEDDS. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.84 and 2.25 year respectively. Conclusions: The results indicate that liquid SMEDDS and solid SMEDDS of tacrolimus, owing to nano-sized, have potential to enhance the absorption of the drug.
44 citations
TL;DR: The present study indicated enormous potential of mucoadhesive buccal patches containing Ivabradine for systemic delivery with an added advantage of circumventing hepatic first pass metabolism.
Abstract: Background: Ivabradine hydrochloride is an anti-anginal drug with a biological half-life of about 2 h and repeated daily administration is needed to maintain effective plasma level. Present investigation of buccal films of Ivabradine hydrochloride is an attempt to avoid the repeated administration and release of drug in more controlled fashion, thereby, to improve the bioavailability. Materials and Methods: Buccal patches were fabricated by solvent casting technique and were evaluated for its physical properties like physical appearance, weight uniformity, thickness, swelling index, surface pH, mucoadhesive time and folding endurance, in vitro and ex vivo release studies. Results: A combination of hydroxypropyl methyl cellulose (HPMC) K15M and K100M with carbopol 940, PEG 6000 gave promising results. Further, the drug content of all the formulations was determined and was found to be uniform. All the formulations were subjected to in vitro release study using phosphate buffer pH 6.6. Patches exhibited drug release in the range of 90.36% ± 0.854 to 98.37% ± 0.589 at the end of six hrs . The best formulations (F2 and F5) containing the composition of HPMC K15-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg and HPMC K100-37.50 mg, carbopol-0.42 mg, PEG6000-16.87 mg, Aspertane-0.28 mg, Tween-0.0023 mg respectively exhibited in vitro drug release of 97.61% ± 0.589 and 98.37% ± 0.114 respectively. The results of ex vivo diffusion using goat cheek pouch revealed that the drug release rate was retarded up to seven hrs. Films prepared with permeation enhancer (Tween 80) showed faster drug release. Finally, stability studies were carried out by using human saliva for the optimized formulation (F2-F5). Conclusion: The present study indicated enormous potential of mucoadhesive buccal patches containing Ivabradine for systemic delivery with an added advantage of circumventing hepatic first pass metabolism. Further work is recommended to support its efficacy claims by long term pharmacokinetic and pharmacodynamic studies in human beings.
29 citations
TL;DR: The study concluded that the developed buccal films have the potential to release ondansetron required for chemotherapy induced acute and delayed emesis.
Abstract: Introduction: Difficulty or inability in swallowing tablets/capsules during or after chemotherapy is common due to chemotherapy induced nausea and vomiting in patients. Buccoadhesive films of ondansetron hydrochloride were prepared for the prevention and treatment of chemotherapy-induced emesis. Films of varying polymeric composition were prepared in order to facilitate initial as well as prolonged drug release that could take care of acute as well as delayed emesis. Materials and Methods: Mucoadhesive films were prepared using polymers such as hydroxypropyl methylcellulose (HPMC) E5, HPMC K100, and Eudragit ® NE 30 D. The effect of concentration of these polymers on physical properties and drug release were studied. All the films were prepared by solvent casting method. In another part of the study, the effect of drug concentration on physical and mucoadhesive properties of film were assessed, keeping the polymer concentration fixed. Results: Films containing HPMC showed good mucoadhesion. Increasing the concentration of Eudragit ® NE 30 D in the films retarded drug release and increased residence time, however, reduced mucoadhesion. At a fixed polymer concentration and ratio, films prepared using an increased drug content showed an increased mucoadhesion. Conclusion: Films prepared using HPMC E5 (1000 mg), HPMC K100 (500 mg), and Eudragit ® NE 30 D (750 mg) provided initial rapid followed by sustained drug release over a period of 6 h. Given the promising results, the study concluded that the developed buccal films have the potential to release ondansetron required for chemotherapy induced acute and delayed emesis.
28 citations
TL;DR: SPH interpenetrating networks with fast swelling and sufficient mechanical strength were prepared, which can be potentially exploited for designing gastroretentive drug delivery devices.
Abstract: Objective: Present investigation was aimed at developing gastroretentive superporous hydrogels (SPHs) having desired mechanical characteristics with sustained release. Materials and Methods: The acrylamide based SPHs of various generations (1 st , 2 nd and 3 rd ) were synthesized by gas blowing technique. The prepared SPHs were evaluated for swelling, mechanical strength studies and scanning electron microscopy studies. Verapamil hydrochloride was loaded into selected SPHs by aqueous drug loading method and characterized via Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD),differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and in vitro drug release studies. Results: SPHs of third generation were observed to have desired mechanical strength with sufficient swelling properties. Integrity of the drug was maintained in hydrogel polymeric network as indicated by FTIR, X-RD, and DSC and NMR studies. Initially, fast drug release (up to 60%) was observed in 30 min in formulation batches containing pure drug only (A, C and E), which was further sustained untill 24 h. Discussion: The increase in mechanical strength was due to the chemical cross-linking of secondary polymer in hydrogel network. The initial burst release was due to the presence of free drug at the surface and later sustained drug release was due to diffusion of entrapped drug in polymeric network. Significant decrease in drug release was observed by the addition of hydroxypropyl methyl cellulose. Conclusion: SPH interpenetrating networks with fast swelling and sufficient mechanical strength were prepared, which can be potentially exploited for designing gastroretentive drug delivery devices.
24 citations
TL;DR: Although significant increment in MS release was observed with CA, addition of 20% w/w FA demonstrated more pronounced and significant increase in drug entrapment as well as release from MS:HPMC:EC (1:1:2) buoyant microspheres, MS release from the prepared microsphere was influenced by changing MS-polymer, MS- polymer-polymers ratio and pH modifier.
Abstract: Introduction: Incorporation of pH modifier has been the usual strategy employed to enhance the dissolution of weakly basic drug from floating microspheres. Microspheres prepared using a combination of both ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) which shows highest release were utilize to investigate the effect of fumaric acid (FA), citric acid (CA), ascorbic acid (AA) and tartaric acid (TA) (all 5-20% w/w) incorporation on metoprolol succinate (MS) release. Materials and Methods: EC, HPMC alone or in combination were used to prepare microspheres that floated in simulated gastric fluid and evaluated for a percent yield, drug entrapment, percent buoyancy and drug release. The higher drug release in combination (MS:HPMC:EC, 1:1:2) was selected for the evaluation of influence of pH modifiers on MS release. CA (5-20% w/w), AA (5-20% w/w), FA (5-20% w/w) and TA (5-20% w/w) were added and evaluated for drug release. Present investigation is directed to develop floating drug delivery system of MS by solvent evaporation technique. Results: The microspheres of MS:HPMC:EC (1:1:2) exhibited the highest entrapment (74.36 ± 2.18). The best percentage yield was obtained at MS:HPMC (1:1) (83.96 ± 1.50) and combination of MS:HPMC:EC (1:1:2) (79.23 ± 1.63). Conclusion: MS release from the prepared microspheres was influenced by changing MS-polymer, MS-polymer-polymer ratio and pH modifier. Although significant increment in MS release was observed with CA (20% w/w), TA (20% w/w) and AA (20% w/w), addition of 20% w/w FA demonstrated more pronounced and significant increase in drug entrapment as well as release from MS:HPMC:EC (1:1:2) buoyant microspheres.
21 citations
TL;DR: With careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed.
Abstract: Objective: The objective of this study was to develop a novel 1 month depot paclitaxel (PTX) microspheres that give a sustained and complete drug release. Materials and Methods: PTX loaded microspheres were prepared by o/w emulsion solvent evaporation technique using the blends of poly(lactic-co-glycolic acid) (PLGA) 75/25, polycaprolactone 14,000 and polycaprolactone 80,000. Fourier transform infrared spectroscopy was used to investigate drug excipient compatibility. Compatible blends were used to prepare F1-F6 microspheres, the process was characterised and the optimum formulation was selected based on the release. Optimised formulation was characterised for solid state of the drug using the differential scanning calorimetry (DSC) studies, surface morphology using the scanning electron microscopy (SEM), in vivo drug release, in vitro in vivo correlation (IVIVC) and anticancer activity. Anticancer activity of release medium was determined using the cell viability assay in Michigan Cancer Foundation (MCF-7) cell line. Results: Blend of PLGA with polycaprolactone (Mwt 14,000) at a ratio of 1:1 (F5) resulted in complete release of the drug in a time frame of 30 days. F5 was considered as the optimised formulation. Incomplete release of the drug resulted from other formulations. The surface of the optimised formulation was smooth and the drug changed its solid state upon fabrication. The formulation also resulted in 1-month drug release in vivo. The released drug from F5 demonstrated anticancer activity for 1-month. Cell viability was reduced drastically with the release medium from F5 formulation. A 100% IVIVC was obtained with F5 formulation suggesting the authenticity of in vitro release, in vivo release and the use of the formulation in breast cancer. Conclusions: From our study, it was concluded that with careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed.
20 citations
TL;DR: Conclusively, cavamax W7 composite ethosomes present themselves as efficient carrier for superior topical delivery of psoralen and have potential for clinical applications in minimizing side effects associated with photosensitivity of Psoralen.
Abstract: Aim: The present research work was aimed to formulate and characterize psoralen-encapsulated cavamax W7 composite ethosomal gel and compare its in vitro and ex vivo behavior against psoralen-cavamax W7-complex reference gel. Materials and Methods: A total of nine formulations of composite ethosomes were prepared by injection method using 3 2 factorial design and entrapment efficiency was designated as dependent variable. Concomitantly, psoralen was complexed with cavamax W7 (1:1 molar ratio) by kneading method and formation of complex was confirmed by Diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). Results: F9 with vesicle size of 183 ± 2.8 nm, and highest % entrapment efficiency of 98.12 ± 1.15 was selected as optimized formulation. Transmission electron microscopy (TEM) revealed uniform and spherical shaped vesicles. The optimized formulation F9 was formulated as carbapol gel and compared against ethosomal gel, psoralen gel, and psoralen cavamax W7 complex gel. The gels were evaluated for permeation characteristics and the rank order was composite ethosomal gel > ethosomal gel > psoralen-cavamax W7 complex gel > psoralen gel. The ethosomal gel (G5) with highest in vitro permeation of 82.48 ± 2.23% was subjected to in vivo Confocal laser scanning microscopy (CLSM) studies using rhodamine B as tracer. The penetration of rhodamine B was uniform, deeper, and two times faster into epidermis than control gel. Conclusion: Conclusively, cavamax W7 composite ethosomes present themselves as efficient carrier for superior topical delivery of psoralen and have potential for clinical applications in minimizing side effects associated with photosensitivity of psoralen.
TL;DR: Sustained release pellets of Budesonide could be prepared by extrusion and spheronization which released the drug in intestinal pH for an intestine to treat inflammatory bowel disease.
Abstract: Introduction: The aim of present work was to develop intestinal-targeted pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and Crohn's disease by extrusion and spheronization method. Current available oral formulations of Budesonide have low efficacy because of the premature drug release in the upper part of the gastrointestinal tract. In this study, a pH-controlled intestinal-targeted pellet of budesonide was established using 3 2 full factorial design by giving an enteric coating with Eudragit S100. Materials and Methods: Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 3 2 full factorial design. The pellets were coated by spray coating technique using Eudragit S100 as an enteric polymer. The pellets were characterized for its flowability, sphericity, friability, and in vitro drug release. Release behaviour was studied in different pH media. The release profile was studied for the mechanism of drug release. Result: The optimized formulation showed negligible drug release in the stomach followed by release for 12 h in the intestinal pH. Differential scanning calorimetry and Fourier Transform Infrared Spectroscopy studies indicated no interaction between drug and polymer. Scanning Electron Microscopy image of coated pellets suggested a uniform and smooth coat over the surface of pellets. Accelerated stability studies showed a stable nature of drug in the formulation. All evaluation parameter showed that pellets were good in spherocity and flowability. Conclusion: Sustained release pellets of Budesonide could be prepared by extrusion and spheronization which released the drug in intestinal pH for an intestine to treat inflammatory bowel disease. A ratio of polymer combination could be decided using a full factorial design.
TL;DR: Ondansetron HCl loaded microbeads can prove to be potential pharmaceutical dosage forms for sustaining the drug release and reducing the dose frequency and are revealed to be most suitable mode of drug delivery for promising therapeutic action.
Abstract: Background : Mucoadhesive beads were fabricated and evaluated for controlled release of an antiemetic drug 'Ondansetron Hydrochloride'. Ondansetron hydrochloride is a serotonin 5-HT 3 receptor antagonist mainly used for the treatment of emesis, which occurs as a side effect of chemotherapy. Materials and Methods: The present work was to fabricate and evaluate ondansetron-loaded microbeads by using chitosan as mucoadhesive and sustained release polymer. Sodium tripolyphosphate (Na-TPP) was used as a cross-linking agent. The microbeads were successfully prepared by ionotropic gelation technique. The particle size, entrapment efficiency, and mucoadhesive strength of drug-loaded formulations was measured by an optical microscope, direct crushing method, and in vitro wash-off method, respectively. Results: Particle size, entrapment efficiency, mucoadhesive strength, and in vitro drug release of optimized formulation was found to be 760.11 ± 1.02 μm, 75.09 ± 2.40%, 95.14 ± 0.27% and 87.45 ± 1.21%, respectively. The data was fitted to different kinetic models to illustrate its anomalous (non-Fickian) diffusion. Conclusions: The results revealed that ondansetron HCl loaded microbeads are most suitable mode of drug delivery for promising therapeutic action. Ondansetron HCl-loaded microbeads can prove to be potential pharmaceutical dosage forms for sustaining the drug release and reducing the dose frequency.
TL;DR: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life and no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed.
Abstract: Introduction: Alginates can be tailored chemically to improve solubility, physicochemical, and biological properties and its complexation with metal ion is useful for controlling the drug release. Materials And Methods: Synthesized N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The synthesized polymeric material exhibited reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives demonstrated pulsed release where change in pH of the dissolution medium stimulated the atenolol release. Conclusion: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life. Although the synthesized derivatives greatly altered the aqueous solubility of sodium alginate, no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed.
TL;DR: Superporous hybrid hydrogels can be promising devices for the sustained delivery of drug candidates to the gastrointestinal region as indicated by DSC, FTIR, X-RD and NMR studies.
Abstract: Objective: Current research was aimed at the development of the drug delivery systems based on the superporous hydrogels (SPH) with the desired swelling and the mechanical properties. Materials and Methods: Superporous hydrogel composites (SPHCs) and superporous hybrid hydrogels (SPHHs) based on the chitosan and the polyacrylamide were synthesized using the gas blowing technique. The prepared hydrogels were evaluated for swelling studies, mechanical strength and scanning electron microscopy. The selected hydrogels were loaded with the drug (verapamil hydrochloride) by aqueous loading method. Drug integrity with in polymeric network was evaluated via fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance ( 1 HNMR) studies. In vitro drug release studies were carried out using the united state pharmacopoeial (USP) dissolution apparatus (type II). Results and Discussion: The mechanical strength was observed to be higher in SPH hybrids in comparison to that in SPHCs while no significant difference was observed in swelling behavior. In situ crosslinking of chitosan with glutaraldehyde (GA) may be responsible for high mechanical strength. The equilibrium swelling time was slight higher in SPHH than in SPHCs. The integrity of pores was maintained in ethanol treated hydrogels as observed in scanning electron micrographs. Whereas, freeze dried SPH samples showed non-uniform pores. No drug polymer interaction was observed as indicated by DSC, FTIR, X-RD and NMR studies. However, the crosslinking of chitosan with GA was clearly indicated by these studies. The in vitro drug release studies from SPH hybrids indicated initial fast release (65%) with in first 2 h and then sustained release at the end of 24 h (95%). The addition of hydroxypropyl methyl cellulose with drug; however, leads to a significant decrease in drug release (56% at the end of 24 h). Conclusion: Superporous hybrid hydrogels can be promising devices for the sustained delivery of drug candidates to the gastrointestinal region.
TL;DR: Based on the observed antimicrobial and wound healing effects, the formulations containing combination of NF and Curcuma longa could be employed as an alternative to commercial silver sulfadiazine 1% cream for making burn wound healing process more effective.
Abstract: Objective: In an attempt for better treatment of bacterial infections and burn wounds, semisolid formulations containing norfloxacin (NF) and natural wound healing agent Curcuma longa were prepared. The rationale behind employing combination of NF and Curcuma longa is to obtain synergistic wound healing effect. The prepared formulations were compared with silver sulfadiazine cream 1%, USP. Materials and Methods: Various ointments containing NF and C. longa were prepared using standard procedures. These formulations were evaluated for antimicrobial activity against various strains of aerobic and anaerobic microorganisms. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. Results: The significant antimicrobial and wound healing effects were demonstrated by formulations which are comparable with silver sulfadiazine 1% cream (P < 0.05). Various morphological changes were observed by histopathology during the study period (days 1, 4, 8 and 12) which also supported the wound healing process. Conclusion: Based on the observed antimicrobial and wound healing effects, the formulations containing combination of NF and Curcuma longa could be employed as an alternative to commercial silver sulfadiazine 1% cream. This innovative mode of formulation can be employed for making burn wound healing process more effective.
TL;DR: It was concluded that the Aloe vera gel acts as an effective gel base to prepare piroxicam gel with high drug loading capacity and improved anti-inflammatory effect.
Abstract: Background: The aim of the study was to develop piroxicam- Aloe vera gel (PAG) formulation and make a pharmacodynamic evaluation of the formulation. Materials and Methods: The gel was prepared by using carbopol 934 as gelling agent and methyl paraben as a preservative in an Aloe vera gel base. The formulated gel was also evaluated for physicochemical parameters like pH, viscosity, drug content, and in vitro diffusion assessment. Pharmacodynamic activity of the formulation was evaluated in Wistar albino rats. The formulated gel was compared with that of similar marketed gel (commercial piroxicam gel (CPG)) against the same parameters. Results: From in vitro studies, an effective drug release from PAG was observed to be 68.17% when compared with that of the CPG (62.71%) at 180 min indicating better drug release from the gel formulated in this study. Percentage inhibition of edema was greater for the preparation of PAG (29.57 mean percent inhibition after 60 min) compared to marketed gel which exhibited 18.3% after 60 min. Conclusion: It was concluded from the results that the Aloe vera gel acts as an effective gel base to prepare piroxicam gel with high drug loading capacity and improved anti-inflammatory effect. From the statistical analysis the formulation of PAG showed better release than the CPG at p < 0.05 level of significance.
TL;DR: Pellets with good surface morphology and smooth texture confirmed by stereo micrographs and HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating.
Abstract: Introduction: The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. Materials and Methods: The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. Results: Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor ( f 1 ) and similarity factor ( f 2 ) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. Conclusions: By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.
TL;DR: The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.
Abstract: Introduction : Verapamil hydrochloride (VH) is a calcium channel blocking agent used in the treatment of hypertension, cardiac arrhythmia and angina pectoris. The short half-life and high frequency of administration of VH makes it a suitable candidate for designing sustained drug delivery system. The aim of the present investigation was to develop a sustained release matrix tablet of verapamil hydrochloride (VH) using ethyl cellulose, methyl cellulose, Eudragit RS 100, hydroxypropyl methylcellulose and carboxymethyl cellulose and to evaluate the drug release kinetics. Materials and Methods: In order to achieve the required sustained release profile, the tablets were prepared by a wet granulation method using avicel PH 101 and magnesium stearate as binder and lubricant, respectively. Results: The formulated tablets were characterized for pre-compression and post-compression parameters and they were in the acceptable limits. The drug release data obtained after an in vitro dissolution study was fitted to various release kinetic models in order to evaluate the release mechanism and kinetics. The criterion for selecting the best fit model was linearity (coefficient of correlation). Drug release mechanism was found to follow a complex mixture of diffusion, swelling and erosion. Furthermore, to minimize the initial burst drug release, batches were coated by using Eudragit RS100 polymer. After coating the tablets, a better release profile of the formulated tablets was expected and the release rate of the drug was compared with the marketed SR tablet of VH. Conclusion: The dosage form holds the potential to control the release rate of drug and extend the duration of action of a drug.
TL;DR: Development of GNPs and M-GNPs will pave the way for reticuloendothelial system uptake of AZT; thus, achieving targeted delivery, selectivity and reduction in associated side effect reduction in acquired immuno defficiency syndrome is concluded.
Abstract: Introduction: The present work was aimed at development and evaluation of zidovudin (AZT) loaded gelatin nanoparticles (GNPs) by simple desolvation method and further couple it with mannose. Material and Methods: Total seven batches of GNPs (A1-A7) were formulated by changing the concentration of polymer gelatin. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency and in- vitro drug release of plain and mannosylated gelatin nanoparticles (M-GNPs) were studied. Results: Scanning electron microscopy (SEM) studies revealed that the average particle size of GNPs and M-GNPs were found to be 394 ± 3.21 and 797.2 ± 2.89 nm respectively (optimised batch A3). It was interesting to note that the average particle size of M-GNPs was more due to anchored mannose, whereas drug entrapment was lesser compared to plain GNPs. Studies have showed drug loading for GNPs and M-GNPs to be 66.56% and 58.85% respectively. Zeta potential studies demonstrated little reduction in solution stability of M-GNPs compared to GNPs. In- vitro drug release studies showed almost 80% release (bimodal) up to 24 h, following Korsmeyer-Peppas release kinetics model (GNPs, r = 0.9760; M-GNPs, r = 0.9712). Conclusions: Hence, it can be concluded that, development of GNPs and M-GNPs will pave the way for reticuloendothelial system uptake of AZT; thus, achieving targeted delivery, selectivity and reduction in associated side effect reduction in acquired immuno defficiency syndrome.
TL;DR: The prepared enteric coated mucoadhesive microspheres of duloxetine hydrochloride may prove to be a potential controlled release formulation of DLX for oral administration.
Abstract: Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3 2 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X 1 ) and stirring speed (X 2 ) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t 24 ). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.
TL;DR: Results showed that the T. polium extract has a wide band of ultraviolet radiation (UV) spectrum absorption ranging from 250 nm to 380 nm, revealing a synergistic action between ZnO and T. Polo, and lengthening their persistence on the skin and contributing to further duration of action.
Abstract: Introduction: Zinc oxide nanoparticles (ZnOn) have been used as carriers and sun-protecting agents for Teucrium polium L. extract to enhance sun protection. ZnOn was synthesized by hydrolyzing zinc acetate using sodium hydroxide with mean particle diameter less than 500 nm. Materials and Methods: Top flowerings of T. polium L. were extracted by percolation method with petroleum ether, chloroform, and 80% methanol consecutively. Methanolic extract was lyophilized and used as a flavonoid-rich fraction. Sunscreen was prepared by the reconstitution of 0.5 g of the lyophilized extract in water and mixing with 0.5 to 2 g zinc-oxide (ZnO). Sun protection factor (SPF) of the aqueous extract of T. polium , the prepared gel, as well as the zinc oxide suspension alone and in combination with each other was determined spectrophotometrically based on a modified Transpore; tape method. Results and Conclusion: Obtained results showed that the T. polium extract has a wide band of ultraviolet radiation (UV) spectrum absorption ranging from 250 nm to 380 nm. SPF of the combination product in the ultraviolet B (UVB) area was greater than 80, revealing a synergistic action between ZnO and T. polium . The adsorption of flavonoids of T. polium on Zinc-oxide nanoparticles (ZnOn) slowed down their release thereby lengthening their persistence on the skin and contributing to further duration of action.
TL;DR: The results of present study demonstrated that the in vitro development of bilayered gastro retentive floating tablets with controlled drug release profile for LM is feasible and reproducible for large scale production in the industry.
Abstract: Aim: The purpose of this study was to prepare lamotrigine (LM) bilayered and single layered floating tablets and to compare their release profiles. Materials and Methods: LM floating tablets were prepared by direct compression method. Drug, hydroxy propyl methyl cellulose K4M, lactose monohydrate and polyvinylpyrrolidone K30 constitute controlled release layer components and floating layer components includes polymers and sodium bicarbonate. The prepared tablets were evaluated for physicochemical parameters such as hardness, friability, weight variation, thickness, floating lag time (FLT), floating time, in vitro buoyancy study, in vitro release studies. The drug-polymer interaction was studied by fourier transform infrared and differential scanning calorimetry. Results and Discussion: The FLT of all the formulations were within the prescribed limits (<3 min). When ethyl cellulose was used as floating layer component, tablets showed good buoyancy effect but eroded within 6-8 h. Hence it was replaced with hydroxypropyl cellulose -M hydrophilic polymer, which showed good FLT and floating duration for 16 h. Formulation LFC4 was found to be optimized with dissolution profile of zero order kinetics showing fickian diffusion. A comparative study of bilayered and single layered tablets of LM showed a highest similarity factor of 83.03, difference factor of 2.74 and t-test (P < 0.05) indicates that there is no significant difference between them. Conclusion: Though bilayered tablet possess many advantages, single layered tablet would be economical, cost-effective and reproducible for large scale production in the industry. However, the results of present study demonstrated that the in vitro development of bilayered gastro retentive floating tablets with controlled drug release profile for LM is feasible.
TL;DR: The in vivo experiments presented effective amelioration from colitis in TNBS-induced animal model of colitis and the toxicity of prednisolone (PD) was reduced significantly as predicted from thymus to body weight ratio of treated animals.
Abstract: Drugs prescribed for the treatment of moderate to severe inflammatory bowel disease (IBD) are associated with number of side effects. Targeted drug delivery is essential for the treatment of inflammatory bowel disease in order to increase efficacy and reduce toxicity. The established delivery system is designed on enzyme and time-based release of poorly soluble prednisolone, a drug of choice for the treatment of moderate to severe inflammatory bowel disease. Their pharmacological evaluation was done in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced model of colitis in rat. The drug was administered once daily for 3 consecutive days. Visible severity of colitis, tissue to bodyweight ratio, tissue histology along with nitric oxide (NO), malondialdehyde (MDA) and myeloperoxidase (MPO) activity of colonic tissue were studied to estimate the efficacy of the drug-loaded delivery system. The highest efficacy was observed for formulation in which Eudragit RS100 (EU) was used along with guar gum (GG) in a ratio 2:5 for the preparation of delivery device. An effective recovery was observed from the study of tissue histology of animals treated with the drug-loaded optimized formulation and the biochemical parameters supported it. The toxicity of prednisolone (PD) was reduced significantly as predicted from thymus to body weight ratio of treated animals. GG and EU RS100 provided a newer bipolymer combination for the colon-targeted delivery of PD which increased its efficacy and reduced the toxic side effects. The in vivo experiments presented effective amelioration from colitis in TNBS-induced animal model of colitis.
TL;DR: The main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets.
Abstract: Introduction: Lacidipine (LCDP) is chemically a 1, 4-dihydropyridine derivative Ca+ 2 channel blocker used as an antihypertensive. Type and extent of packaging have a strong influence on the photo-stability of the 1,4-dihydropyridine derivatives. In standard, light protection of drug substance/drug product can be obtained either by use of an opaque additive in the formulation that competitively absorbs or reflects light reaching the sample and/or by blocking the access of light to the drug through external protection by packaging. Materials and Methods: External protection by covering tablets with an opaque film coating involving a light-reflecting inorganic pigment such as titanium dioxide and/or by using an opaque impermeable packaging material was an appropriate suitable option for establishing photo-stability. Thus, the main objective of the present study was to optimize the % level of film coating in LCDP core tablets, and selection of a final packaging material and its respective extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets. Results and Conclusion: The main objective (% level of film coating) was optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film-coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative analysis at the end of light exposure testing. The other objective (extent of drug product packaging) was established successfully by assessing whether or not an acceptable change has occurred at the end of the light exposure testing of the LCDP film-coated tablets in a direct exposure study or a primary immediate pack and/or secondary marketing pack.
TL;DR: This quality risk management (QRM) study is to provide a sophisticated “robust and rugged” Fluidized Bed Process (FBP) for the preparation of LCDP tablets with desired quality (stability) and performance (dissolution) by quality by design (QbD) concept.
Abstract: Introduction: Lacidipine (LCDP) is a very low soluble and highly biovariable calcium channel blocker used in the treatment of hypertension. To increase its apparent solubility and to reduce its biovariability, solid dispersion fluid bed processing technology was explored, as it produces highly dispersible granules with a characteristic porous structure that enhances dispersibility, wettability, blend uniformity (by dissolving and spraying a solution of actives), flow ability and compressibility of granules for tableting and reducing variability by uniform drug-binder solution distribution on carrier molecules. Materials and Methods: Main object of this quality risk management (QRM) study is to provide a sophisticated "robust and rugged" Fluidized Bed Process (FBP) for the preparation of LCDP tablets with desired quality (stability) and performance (dissolution) by quality by design (QbD) concept. Results and Conclusion: This study is principally focusing on thorough mechanistic understanding of the FBP by which it is developed and scaled up with a knowledge of the critical risks involved in manufacturing process analyzed by risk assessment tools like: Qualitative Initial Risk-based Matrix Analysis (IRMA) and Quantitative Failure Mode Effective Analysis (FMEA) to identify and rank parameters with potential to have an impact on In Process/Finished Product Critical Quality Attributes (IP/FP CQAs). These Critical Process Parameters (CPPs) were further refined by DoE and MVDA to develop design space with Real Time Release Testing (RTRT) that leads to implementation of a control strategy to achieve consistent finished product quality at lab scale itself to prevent possible product failure at larger manufacturing scale.
TL;DR: The decontamination studies proved the potential of EDTA to remove the radiological contaminants effectively and optimized and develop self-usable radiation decontaminant cream formulation.
Abstract: Background: Increased use of the radioactive materials in the field of research, medical, nuclear power plant and industry has increased the risk of accidental exposure Intentional use of the radioisotopes by terrorist organizations could cause exposure/contamination of a number of the population In view of the accidental contamination, there is a need to develop self-usable decontamination formulations that could be used immediately after contamination is suspected Materials and Methods: Present work was planned to optimize and develop self-usable radiation decontamination cream formulation Various pharmaceutical parameters were characterized 99m Tc- sodium pertechnetate was used as radiocontaminant Static counts were recorded before and after decontamination using single photon emission computed tomography Results: Decontamination efficacy of the cream was found to be 42% ± 3% at 0-05 h after the exposure Primary skin irritancy test was satisfactory as no erythema or edema was observed visually after 2 weeks of the formulation application Conclusion: The decontamination studies proved the potential of EDTA to remove the radiological contaminants effectively
TL;DR: The results of the study indicate that ACF could be administered topically by using iontophoresis from a suitably formulated gel for effective control of pain and inflammation.
Abstract: Introduction: Iontophoresis was used to enhance the delivery of aceclofenac (ACF) from topical gels formulated with various polymers for the purpose of relieving pain and inflammation. Materials and Methods: Gels were formulated from hydroxypropyl methyl cellulose (HPMC), carbopol 934P, and sodium carboxymethyl cellulose (NaCMC). The formulations were evaluated for cathodal iontophoretic delivery of ACF through excised rat abdominal skin at three levels of current density of 0.5, 0.6 and 0.7 mA/cm 2 . The in vivo effectiveness of the drug delivered passively as well as under the influence of iontophoresis at pH 7.4 at a current density of 0.5 mA/cm 2 was also investigated using male Albino rats with carrageenan induced paw edema. Results and Discussion: In the ex vivo studies, though it was clear that iontophoresis significantly increased drug permeation through the excised skin from all formulations; the percentage drug permeated from HPMC gels was superior to that from carbopol 934P or NaCMC gels but increased with an increase in the current density only for the former. The steady state flux, permeability coefficient, enhancement factor were significantly greater from HPMC gels than from the gels of the ionic polymers due to the interference of competitive ions. With iontophoresis, the carrageenan induced paw edema was significantly reduced by 61.53% (P Conclusion: The results of the study indicate that ACF could be administered topically by using iontophoresis from a suitably formulated gel for effective control of pain and inflammation.
TL;DR: It may be concluded that polypill released the metoclopramide immediately prior to 6-mercaptopurine, which resulted in the reduction of emesis caused by oral chemotherapy.
Abstract: Introduction: The present investigation was to develop a polypill of 6-mercaptopurine and metoclopramide. A polypill with delayed release granules of an anticancer and immediate release mucoadhesive tablet of antiemetic may result in the reduction of emesis caused by oral chemotherapy. Materials and Methods: 6-Mercaptopurine granules were prepared by wet granulation process. Chitosan, hydroxypropyl methylcellulose, and ethylcellulose were used as individually as delayed release polymers. Seven granule formulations (F1-F7) were prepared and evaluated for flow properties and drug content. Immediate release mucoadhesive tablets of metoclopramide were prepared by direct compression technique using pectin and PVPK-40 as mucoadhesive polymers. Three formulations of pectin (L1-L3) and three formulations of PVPK40 (M1-M3) were prepared using lactose, magnesium stearate, and mannitol and talc as diluent and glidant, respectively. Tablets were evaluated for weight variation, hardness, friability, drug content, ex vivo mucoadhesion time, and in vitro dissolution studies. Results: Formulation F2, F4, F5, and F7 showed maximum drug content. Formulation F7 exhibited the drug release up to 2 h and was selected as the best delayed release formulation. All formulations of metoclopramide showed good drug content ranging from 97.6 % to 100.6%. Formulation M2 among tablets prepared with PVP exhibited desired mucoadhesion time of 15.33 min which prolongs the duration of drug release in gastric pouch of the male Wistar rats. Both the selected formulations F7 and M2 were filled into body of capsule size 0 and capsule was evaluated for technological properties. Conclusion: It may be concluded that polypill released the metoclopramide immediately prior to 6-mercaptopurine.