Showing papers in "Recent Patents on Drug Delivery & Formulation in 2019"

Nutraceuticals' Novel Formulations: The Good, the Bad, the Unknown and Patents Involved.

Abstract: Traditional nutraceuticals and cosmeceuticals hold pragmatic nature with respect to their definitions, claims, purposes and marketing strategies. Their definitions are not well established worldwide. They also have different regulatory definitions and registration regulatory processes in different parts of the world. Global prevalence of nutraceuticals and cosmeceuticals is noticeably high with large market share with minimal regulation compared to traditional drugs. The global market is flooded with nutraceuticals and cosmeceuticals claiming to be of natural origin and sold with a therapeutic claim by major online retail stores such as Amazon and eBay. Apart from the traditional formulations, many manufacturers and researchers use novel formulation technologies in nutraceutical and cosmeceutical formulations for different reasons and objectives. Manufacturers tend to differentiate their products with novel formulations to increase market appeal and sales. On the other hand, researchers use novel strategies to enhance nutraceuticals and cosmeceuticals activity and safety. The objective of this review is to assess the current patents and research adopting novel formulation strategies in nutraceuticals and cosmeceuticals. Patents and research papers investigating nutraceutical and cosmeceutical novel formulations were surveyed for the past 15 years. Various nanosystems and advanced biotechnology systems have been introduced to improve the therapeutic efficacy, safety and market appeal of nutraceuticals and cosmeceuticals, including liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers. This review provides an overview of nutraceuticals and cosmeceuticals current technologies, highlighting their pros, cons, misconceptions, regulatory definitions and market. This review also aims in separating the science from fiction in the nutraceuticals and cosmeceuticals development, research and marketing.

Nanocapsules for Drug Delivery: An Updated Review of the Last Decade.

Abstract: Background For the past few decades, there has been considerable research interest in drug delivery strategies using nanoparticulate systems as carriers for a wide range of active pharmaceutical ingredients. Objective It is known that nanoparticulate drug delivery systems comprise a wide variety of dosage forms including nanospheres, micelles, solid lipid nanoparticles, nanoliposomes, dendrimers, magnetic nanoparticles, and nanocapsules. Methods This review describes nanocapsule preparation techniques and their applications for the treatment of several diseases using patents and examples from the literature. Results Nanocapsules are vesicular systems consisting of an inner liquid core (aqueous/oily) surrounded by a polymeric wall that has immense potential as drug carriers because of the many advantages like improving poor aqueous solubility, stabilizing drugs by protecting the molecule from the environment, providing the desired pharmacokinetic profile, allowing controlled release, as well as facilitating oral administration. Conclusion The present study discusses and summarizes patents related to preparation methods of and recent studies from the last 10 years on nanocapsules as drug delivery systems.

Nanosuspension Technology: Recent Patents on Drug Delivery and their Characterizations.

Abstract: Background Nanosuspension has arisen as a remunerative, lucrative as well as a potent approach to improve the solubility and bioavailability of poorly aqueous soluble drug entities. Several challenges are still present in this approach which need more research. The prime aim of this review is to identify such challenges that can be rectified in the future. Methods Through this review, we enlighten the recent patents and advancement in nanosuspension technology that utilize the different drug moieties, instruments and characterization parameters. Results Nanosuspension has been found to possess great potential to rectify the several issues related to poor bioavailability, site-specific drug delivery, dosing frequency, etc. In the past decade, nanosuspension approach has been complementarily utilized to solve the developed grievances, arisen from poorly soluble drugs. But this field still needs more attention to new discoveries. Conclusion Nanosuspension contributes a crucial role in administering the different drug entities through a variety of routes involving oral, transdermal, ocular, parenteral, pulmonary, etc. with solving the different issues. This review also confirms the significance of nanosuspension in safety, efficacy, and communal as well as the economic expense associated with healthcare.

Scientific Papers and Patents on Substances with Unproven Effects. Part 2.

Abstract: Several examples are discussed in this review, where substances without proven effects were proposed for practical use within the scope of evidence-based medicines. The following is discussed here: generalizations of the hormesis concept and its use in support of homeopathy; phytoestrogens and soy products potentially having feminizing effects; glycosaminoglycans for the treatment of osteoarthritis and possibilities of their replacement by diet modifications; flavonoids recommended for the treatment of chronic venous insufficiency and varicose veins; acetylcysteine as a mucolytic agent and its questionable efficiency especially by an oral intake; stem cells and cell therapies. In conclusion, placebo therapies can be beneficial and ethically justifiable but it is not a sufficient reason to publish biased information. Importantly, placebo must be devoid of adverse effects, otherwise, it is named pseudo-placebo. Therapeutic methods with unproven effects should be tested in high-quality research shielded from the funding bias. Some issues discussed in this review are not entirely clear, and the arguments provided here can initiate a constructive discussion.

Nanocarriers For Vaginal Drug Delivery.

Abstract: Background Vaginal drug delivery approach represents one of the imperative strategies for local and systemic delivery of drugs. The peculiar dense vascular networks, mucus permeability, and range of physiological characteristics of the vaginal cavity have been exploited for therapeutic benefit. Furthermore, the vaginal drug delivery has been curtailed due to the influence of different physiological factors like acidic pH, constant cervical secretion, microflora, cyclic changes during periods along with turnover of mucus of varying thickness. Objective This review highlights advancement of nanomedicine and its prospective progress towards the clinic. Methods Relevant literature reports and patents related to topics are retrieved and used. Result The extensive literature search and patent revealed that nanocarriers are efficacious over conventional treatment approaches. Conclusion Recently, nanotechnology based drug delivery approach has promised better therapeutic outcomes by providing enhanced permeation and sustained drug release activity. Different nanoplatforms based on drugs, peptides, proteins, antigens, hormones, nucleic material, and microbicides are gaining momentum for vaginal therapeutics.

Pharmaceutical Cocrystal: A Novel Approach to Tailor the Biopharmaceutical Properties of a Poorly Water Soluble Drug.

Abstract: Background The present study reports the formation of a cocrystal of candesartan with the coformer methyl paraben, its characterization and determination of its bioavailability. Candesartan is a poorly water-soluble drug having an anti-hypertensive activity. The recent patents on the cocrystals of the drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib (WO2015170345A1), and Valsartan (CN102702118B) for enhancement of solubility, helped in selection of the drug for this work. Methods Candesartan cocrystal was prepared by solution crystallization method. The formation of a new crystalline phase was characterized by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) and Powder X-ray Diffraction (PXRD) studies. Saturation solubility studies were carried out in ethanol: water (50:50 % v/v) mixture. The dissolution studies were conducted in 900 ml of phosphate buffer at pH 7.4(I.P.) with 0.7% w/w of Tween 20 at 50 rpm, maintained at a temperature of 37±0.5°C in a USP type II dissolution apparatus. The pharmacokinetic behavior of candesartan and its cocrystal was thereof investigated in male Wistar rats. Results There was 6.94 fold enhancement in the solubility of candesartan after its cocrystallization. The dissolution profile of the cocrystal exhibited significant improvement in solubility at 60 and 120 minutes and it remained stable in ethanol: water (50:50%v/v) mixture for 48 h as confirmed by PXRD studies. The AUC0-24of the cocrystal was found to be increased by 2.9 fold in terms of bioavailability as compared to the pure drug. Conclusion The prepared cocrystal was found to be relatively more soluble than the pure drug and also showed an enhanced oral bioavailability as compared to the pure drug.

Design, Development and In vitro/Ex vivo Evaluation of Mucoadhesive Buccal Film of Benzydamine Hydrochloride for the Effective Treatment of Aphthous Stomatitis.

Abstract: Background During the recent two decades, the development of mucoadhesive drug delivery system has been gained tremendous importance to cure many recurrent diseases of the oral cavity. The drug delivery through the buccal route is quite challenging due to limited absorption area, movements of the target region and regular flow of saliva lead to the sub-therapeutic drug level in the buccal region. Objective The aim is to develop unidirectional release mucoadhesive buccal film for the mucosal delivery of Benzydamine Hydrochloride (WO2016126217Al, EP0812193B1) and evaluate the effects of a different grade of HPMC polymer (US5980942A) with the presumption to prolong the residence time and therapeutic effectiveness at the target site. Methods Mucoadhesive buccal films were prepared by solvent casting evaporation method by employing different grades of HPMC as mucoadhesive and rate controlling polymer. Total twenty-four formulations were developed using ethyl cellulose as a backing layer. The prepared films were subjected to various physicochemical parameters. Results The physicochemical parameters were found to be varied according to the type and concentration of polymer used. On the basis of in vitro drug release, desired ex-vivo mucoadhesive time, mucoadhesive force the formulations F4, F9, F14 and F19 were subjected to ex vivo drug permeation study. The F14 film containing 1% w/v of HPMC K50M was considered optimized final formulation due to higher ex vivo drug permeation. Drug-excipient compatibility was confirmed by FTIR and DSC. XRD of final formulation revealed the amorphous nature of drug. SEM indicated the perfect binding between backing and adhesive layer. Conclusion The developed mucoadhesive buccal film having adequate physicochemical properties was capable to provide prolonged residence time and sustained delivery as compared to existing conventional therapies.

Clinical Application of Polysialylated Deoxyribonuclease and Erythropoietin

Abstract: Background While protein therapeutics are invaluable in managing numerous diseases, many require frequent injections to maintain therapeutically effective concentrations, due to their short half-life in circulation PolyXen™, a platform and patented technology employing biodegradable, non-immunogenic and hydrophilic Polysialic Acids (PSA) for drug delivery, is being utilized to overcome such limitations, thereby potentially enabling the clinical utility of a broad range of protein therapeutics Here, we report the recent progress on two development candidates, polysialylated deoxyribonuclease I (PSA-DNase) and polysialylated erythropoietin (PSA-EPO) Methods and results Chemical polysialylation of DNase I (DNase) using PSA with different chain length at various conjugation sites led to improved stability against proteases and thermal stress, and slightly reduced enzymatic activity Polysialylation of EPO resulted in retention of protein structure and PSA-EPO remained biologically active PSA-EPO had a significantly prolonged circulating half-life (eg t1/2 of PSA-EPO = ~400 h in patients after subcutaneous administration, aimed for once monthly administration, vs t1/2 of EPO = ~22 h; administered twice or thrice weekly), and retained in vivo efficacy Conclusion This approach has been clinically validated in phase I (in healthy volunteers) and II studies of PSA-EPO [for managing anemia in patients with chronic kidney disease (CKD)]

Antibacterial and In Vitro Growth Inhibition Study of Struvite Urinary Stones Using Oxalis corniculata Linn. Leaf Extract and its Biofabricated Silver Nanoparticles

Abstract: Background Herbal drugs are gaining exponential scientific recognition due to their distinct advantages In the last 2-3 decades, a gradual increase in worldwide patents on herbal nanoformulations has been noted to address the solubility and bioavailability issues of phytoceuticals Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO46H2O) is among the important urinary infection stones causing painful urological ailment These smaller stones may bind together to form bigger staghorn calculus Urinary tract infections caused by some gram positive and gram negative bacteria further enhance the chance of formation of such stones Oxalis corniculata Linn is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones However, there is no scientific evidence to relate the use of O corniculata against struvite kidney stones Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn leaves and its biofabricated silver nanoparticles (AgNPs) was studied Methods The aqueous extract of O corniculata was prepared by Soxhlet extraction AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies Antibacterial activity of the aqueous extract and the silver nanoparticles was tested against E coli (gram negative) and S aureus (gram positive) species Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles Results The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs Conclusion The present work confirms the inhibitory activity of the aqueous extract of edible O corniculata and its biofabricated silver nanoparticles against urinary tract infection (UTI) causing bacteria and urolithiasis Therefore, the consumption of O corniculata in our daily diet may reduce the risk of UTI and urolithiasis

Mesoporous Silica Nanoparticles: A Versatile Platform for Biomedical Applications.

Abstract: Background Nanotechnology-based drug delivery approach has emerged as a promising field, where different kinds of formulations are developed for therapeutic applications. Inflowing of nanomedicine developed through various biomaterials appears to be a game changer in the domain of pharmaceutical and biotechnological industries. Nanomedicines propose to overcome the major constraints of conventional medicine of low solubility and stability, non-adequate pharmacokinetic profiles and side effects. Objectives Mesoporous Silica Nanoparticles (MSNs) have garnered significant attention in biomedical applications for its multifunctionality. The porous structure of MSNs provides the opportunity for heavy drug loading, controlled release and ligand functionality. From last decades, a lot of interest has been generated owing to the better drug delivery attributes of MSNs to introduce unique biological effects for its suitable therapeutic application. Methods The review article gives an insight into the current advancement of usage of MSNs in drug delivery for cancer, non-cancer and biosensors based biomedical applications along with technology that is protected by patents. Conclusion The future success of MSNs is widened because of their valuable characteristic that easily combines with various functionalities which would display enormous potential translational possibilities.

Role of Porous Carriers in the Biopharmaceutical Performance of Solid SMEDDS of Canagliflozin.

Abstract: Objective The aim of the present investigation entails the development of solid SMEDDS for improving the oral bioavailability of canagliflozin using porous carriers. The previous patent (WO2017046730A1) was based on enhanced solubility of canagliflozin through co-crystal formation. Methods Preconcentrates were prepared by employing Lauroglycol (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) and successfully adsorbed onto various hydrophilic and hydrophobic carriers. The prepared solid SMEDDS were characterized for various parameters to determine the optimized formulation. In vitro, ex vivo and in vivo studies were carried out to determine drug release kinetics, permeation and absorption rate, respectively. Stability of the formulation was investigated at 45°C/75% RH. Results The solid preconcentrates prepared with hydrophobic carriers exhibited desired attributes in a uniform range. Neusilin adsorbed solid SMEDDS (S(N)SMEDDS) portrayed enhanced amorphization in XRD and DSC studies and found to be physically compatible in FTIR studies. SEM revealed colloidal particles having spherical morphology with negligible aggregation. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.72, 5.85, 4.51 and 3.0-fold, respectively, as compared to pure drug. TEM of reconstituted SMEDDS indicated nano-sized globules with negligible coalescence. Enhanced in vitro dissolution rate of optimized solid SMEDDS manifested in bioavailability enhancement of 167.54% and 188.98%, as compared to pure drug and marketed product. These studies further substantiate the lymphatic uptake of SMEDDS through chylomicron flow blocking approach. Establishment of Level A IVIVC showed a uniform correlation between the in vitro dissolution efficiency and in vivo pharmacokinetic parameters. Conclusion The present investigation reveals the immense potential of solid SMEDDS in augmenting the oral bioavailability profile of poorly water-soluble drug canagliflozin.

Comparative Study on Photodynamic Activation of Ortho-Toluidine Blue and Methylene Blue Loaded Mesoporous Silica Nanoparticles Against Resistant Microorganisms.

Abstract: AIMS AND BACKGROUND The number of pathogenic microorganisms has been increasing over the years, and so as resistance of these microorganisms are developing against various antibiotics. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. Recent patents on structured silver mesoporous silica nanoparticles having antimicrobial activity (WO2010/071831 A2), photosensitiser modified core-shell structure nanocomposites (CN 103536935(A)), and Chitosan-coated magnetic mesoporous silica nanoparticles (MSN) (CN 104785214(A)) helped in selecting method of synthesis of MSN and photosensitizers. MATERIALS AND METHODS MSN were synthesised by Sol-Gel method and amino functionalised (APTES). Methylene blue (MB) and ortho-toluidine blue (O-TB) were used as photosensitisers. Different batches were synthesised. The final product was characterised by using FTIR, BET, SEM, time resolved fluorescence. The photosensitiser loaded MSN were illuminated by LED based lamp emitting red light at 620± 20nm for different time lengths viz 15 min and 30 mins. Fluorescence studies and antimicrobial assays were carried out as per 72 well plate method I.P, 2014 using, gram negative E. coli (ATCC no. 8739), S. aureus (ATCC no. 7447) and gram positive P. aeruginosa (ATCC no. 9027) pathogenic microorganisms. RESULTS MB and O-TB were successfully adsorbed on APTES functionalised MSN. Different exposure time length of the photosensitisers to red light showed different zone of inhibition. MB and O-TB loaded MSN showed significant increase in zone of inhibition after irradiation as compared to MB and O-TB loaded on MSN without exposure to light. CONCLUSION MB and O-TB adsorbed on APTES functionalized mesoporous silica nanoparticles were capable of efficiently inactivating E. coli, P. aeruginosa, S. aureus bacteria upon exposure to red light (620± 20nm wavelength) at a much lower concentration. Mesoporous silica nanoparticles played an important role in aPDT due to their high surface area and porous structure. Also, APTES functionalization resulted in the pore expansion of MSN, thereby increasing the loading capacity of the photosensitizer on MSN. From the results obtained it can be concluded that O-TB loaded MSN showed higher activity against gram negative and positive microorganisms microorganism as compared to that of MB.

Synthesis and Characterization of Valacyclovir HCl Hybrid Solid Lipid Nanoparticles by Using Natural Oils.

Abstract: Background The Jojoba Simmondsia Chinensis oil is used as one of the main ingredients which has an antioxidant, moisturizing and stabilizing activity. Likewise, grape seed (Vitis vinifera) oil is also used in this preparation which also has some remarkable medicinal properties such as antioxidant, astringent and is also used as a moisturizer. The Valacyclovir Solid Lipid Nanoparticles (SLN) are prepared in combination. Objective The prime objective of the study was to prepare a nanodispersion with good stability indicating zeta potential. The formulations were prepared by varying concentrations of jojoba oil and grape seed oil which form the hybrid nanoparticles with the drug. Methods The high-pressure hot-homogenization technique was used to prepare the nanoparticles. The prepared nanoparticles were subjected to characterization analysis such as Mean particle size, Zaverage, and Zeta potential by using Dynamic Light Scattering (DLS) and Photon Correlation Spectroscopy (PCS). The best formulation was subjected to Transmission Electron Microscopy (TEM) technique for surface morphology and other characterizations. The crystalline pattern of the drug alone, drug-loaded nanoparticles and nanoparticles without the drug was studied by XRD. The drug excipients compatibility studies were performed by using Fourier-Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry and (DSC). The other factors such as in vitro drug release, and % drug entrapment efficiency were studied by using suitable methods. Results The results demonstrated that the particles are in nano range with good stability with appreciable Zeta potential (-48.2±mV). The selected formulations were analyzed for MPS which demonstrated the value of 306.7±183.4 and 416.5±289.3. The best formulation VNP5 demonstrated the Bellshaped curve and confirmed the uniform distribution. Conclusion Based on the patents, it was demonstrated that valacyclovir is widely used in the treatment and prophylaxis of viral infections in human, particularly infections caused by the herpes group of viruses. Valacyclovir is an effective drug for the treatment of cold sores.

Self-Emulsifying Drug Delivery System of Simvastatin: Formulation Development, Optimization by Box- Behnken Design, In-Vitro and In-Situ Single-Pass Intestinal Perfusion (SPIP) Studies.

Abstract: PURPOSE The purpose of the study was formulation development, optimization and evaluation of a Self-Emulsifying Drug Delivery System (SEDDS) of Simvastatin (SIM) for improvement in dissolution and bioavailability of SIM. Solubility enhancement of Biopharmaceutical Classification System (BCS) Class-II drugs is a burning topic and attracting various publications and patents regarding different strategies employed for improvement of dissolution viz., USOO5340591A (Solid dispersion), US005472954A, US005646131A (complexation), USOO5858410A (Nanosuspensions), USOO5874029A (micronization) US2008.00095O2A1 (Solid composites), US2008O146640A1 (Prodrug) US 2009001 1009 A1 (nanocapsules), etc. Methods: SEDDS was prepared on the basis of solubility studies employing Capmul MCM EP as lipid and Cremophor ELP as surfactant. Box-Behnken design was implemented for optimization by using lipid concentration, surfactant concentration and mixing time as dependent variables and their impact was observed on particle size, poly dispersity index (PDI) and drug released in 15min. Optimized formulation was evaluated for particle size, PDI, zeta potential, emulsification time, transmittance, invitro drug release and in situ Single-Pass Intestinal Perfusion (SPIP) studies. RESULTS For optimized formulation, OF1 value of particle size, PDI, zeta potential, emulsification time, transmittance and percent in-vitro release were 162±14.32nm, 0.19±0.01, -22.3 ±1.1mV, 93±3.11 sec, 99.45±4.35 % and 99.43± 5.6 % in 30 min respectively. In-situ SPIP studies were performed on Wistar rats and the value of predicted fraction absorbed for humans was found to be 0.98. CONCLUSION SIM SEDDS was successfully developed and evaluated for in-vitro & in-vivo parameters. All the evaluated parameters were in tolerable limits. In vitro release studies from optimized formulation, OF1, exhibited maximum drug release when compared to SIM API and marketed preparation. Moreover, the predicted value of fraction absorbed (Fa) in humans by in-situ SPIP method was also in agreement with in-vitro dissolution studies thus, confirming SEDDS as a suitable drug delivery system for solubility enhancement of SIM.

Bilayer tablet based chronotherapeutics in the management of nocturnal asthma: an overview.

Abstract: BACKGROUND Asthma is a common ailment with a larger circadian difference. Nocturnal Asthma (NA) is an inconstant exacerbation of asthmatic condition related to the rise in warning sign during the night time and there is a need for its treatment addressing air route alertness and decline in lung functions. These symptoms are linked to sleep or known as circadian events. Chronotherapeutics is a management system based on an in-vivo drug accessibility programmed to check the rhythms of ailment in a direction to improve the therapeutic outcomes by suppressing the side effects. This review aims to provide an overview of NA, chronotherapeutics for the treatment of NA, bilayer tablets, and advanced techniques involved in the fabrication of bilayer tablets. The review also discusses some of the related patents. METHODS Relevant literature about the latest developments and updated information related to NA, chronotherapeutics and bilayer tablets has been very widely searched on different biomedical literature programs such as Google, Web of Science, PubMed portals, etc. Bilayer tablet mediated chronotherapy has gained significant attention and consideration as it is developed and fabricated based on the body's circadian rhythm. Bilayer tablets can deliver the bioactive compounds at an appropriate time, place as well as amount and site. RESULTS Available literature advocated that the bilayer matrix tablet containing a single drug in the sustained release film and fast releasing film, may be beneficial for the chronic diseases like asthma, migraine, diabetes, hypertension and inflammation which usually require immediate as well as maintained therapeutic effect. CONCLUSION The application of nanotechnology in the arena of medicine will transform the diagnosis and treatment strategies of a wide range of diseases in the upcoming years. The findings of this review confirm the importance of bilayer tablet based chronotherapy in nocturnal asthma.

A Review on Enteric Coated Pellets Composed of Core Pellets Prepared by Extrusion-Spheronization.

Abstract: Enteric coated dosage form bypasses the stomach and releases the drug into the small intestine. Advantages of enteric coated pellets in comparison with enteric coated tablets are a) Pellets provide rapid onset of action and faster drug release due to the smaller size than tablets and b) Pellets exhibit less residence time of acid-labile drugs in the stomach compared to tablets. Dosage form coat can be damaged by longer resistance time in the stomach. The present review summarizes the current state of enteric coated pellets where core pellets are prepared by extrusion-spheronization technique and the enteric coating is applied in a fluidized bed processor. Two approaches are involved in the preparation of core pellets. In the first approach, a mixture of drug and excipient(s)/co-processed excipient is passed through extruders to prepare core pellets. In the second approach, excipient core pellets are prepared by extrusion technique and the drug is layered onto it before the enteric coating. The excipients present in the core pellets decide immediate or extended release of drug in the intestine. The coprocessed excipient pellets provide less batch variability and provide a platform for layering of many drugs before enteric coating. Some patents included enteric coating pellets [CN105456223 (A), CN105596310 (A), CN105616371 (A), CN105663095 (A), CN101611766B, CN106511862 (A), CN106668018 (A), CN106727381 (A), CN106924222 (A), TW200624127 (A), US 2017/0165248A1, US 2017/0224720A1] are discussed.

Preparation, Characterization and In Vivo Assessment of Repaglinide Nanosuspension for Oral Bioavailability Improvement

Abstract: Aims and background The objective of the study was to improve the bioavailability of poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of drug and polymer. Methods Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH. The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study and stability study. Results RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ± 15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by 1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored at 5°C ± 3°C. Conclusion The outcomes of the study revealed significant enhancement in dissolution rate and oral bioavailability of RPG due to size reduction to nano range by HPH.

Progress in Drug and Formulation Development for the Chemoprevention of Oral Squamous Cell Carcinoma: A Review.

Abstract: Background Cancer is a life-threatening global problem with high incidence rates. Prioritizing the prevention of cancer, chemopreventive agents have drawn much attention from the researchers. Objective This review focuses on the discussion of the progress in the development of chemopreventive agents and formulations related to the prevention of oral cancer. Methods In this perspective, an extensive literature survey was carried out to understand the mechanism, control and chemoprevention of oral cancer. Different patented agents and formulations have also exhibited cancer preventive efficacy in experimental studies. This review summarizes the etiology of oral cancer and developments in prevention strategies. Results The growth of oral cancer is a multistep activity necessitating the accumulation of genetic as well as epigenetic alterations in key regulatory genes. Many risk factors are associated with oral cancer. Genomic technique for sequencing all tumor specimens has been made available to help detect mutations. The recent development of molecular pathway and genetic tools has made the process of diagnosis easier, better forecast and efficient therapeutic management. Different chemical agents have been studied for their efficacy to prevent oral cancer and some of them have shown promising results. Conclusion Use of chemopreventive agents, either synthetic or natural origin, to prevent carcinogenesis is a worthy concept in the management of cancers. Preventive measures are helpful in controlling the occurrence or severity of the disease. The demonstrated results of preventive agents have opened an arena for the development of promising chemopreventive agents in the management of oral squamous cell carcinoma.

Review of Recent Patents and Developments in Skeletal Muscle Regeneration.

Abstract: Skeletal muscle is a highly-specialized tissue that is capable of contractile function and able to withstand and adapt to daily mechanical and physiological stress. Musculoskeletal disorders, including muscular dystrophies, result in chronic pain and disability, reduced quality of life, burden on family, and increased healthcare costs. Although several mechanisms have been identified for muscle injury and regeneration, mechanisms of these diseases are poorly understood, and targeted and effective pharmacologic treatment(s) are not available. More research is needed in this area in order to develop effective treatment regimens. The purpose of this review is to discuss known mechanisms of muscle injury and repair, and highlight some recent patents and research developments for treatment of skeletal muscle disorders.

Montelukast Sodium Formulation Containing Green Tea Extract to Reduce the Oxidative Stress in Guinea Pig Model of Chronic Allergic Asthma.

Abstract: AIM AND BACKGROUND The rationale of this study is that, treatment of asthmatic Guinea pig with combined administration of Montelukast sodium and Green Tea Extract (GTE) as a single capsule will mitigate the inflammatory injury in the airways and weaken the asthmatic response. Recent patents for the treatment of asthma researched a polyphenolic alternatives for antiasthmatic combination therapy, especially for those patients who remains unresponsive or poorly responsive for current asthma therapy (US7232585B2). Synergistic activity of green tea polyphenols and therapeutic, prophylatic agents are also reported in some recent patents (US20120172423A1, US20150320696A1). The present work is therefore aimed, to study the effect of Montelukast Sodium capsules coformulated with GTE on oxidative stress markers including Malondialdehyde (MDA), Glutathione (GSH) in different organs and Oxygen Radical Absorbance Capacity (ORAC) assay in plasma. MATERIALS AND METHODS Guinea pigs were placed in histamine chamber and exposed to an aerosol challenge of 0.2% w/v histamine dihydrochloride in distilled water using pressurized air driven nebulizer at a pressure of 0.05 MPa-0.106 MPa for one week. After that, they were divided in to four groups of three each; control, asthmatic control, asthmatic treated with marketed preparation and asthmatic received developed capsules. After oral administration of formulations for three days, pigs were scarificed and oxidative stress markers level including cytoarchitectural manifestation in tissues was studied. RESULTS In comparison with the healthy control group, MDA level of the asthmatic animal liver and lung was found to be elevated as 0.059 ± 0.031(p < 0.002) and 0.802 ± 0.310 (p < 0.005) respectively, whereas GSH level was declined as 13.223 ± 1.485 (p < 0.0001) in liver and 3.037 ± 0.282 (p < 0.0004) in lung tissues. TAC of asthmatic animal plasma was low as 2.132 ± 0.986 mM Trolox Eq/L (p < 0.009). The level of these biomarkers reverts back towards normal after treatment with marketed and developed formulation, although treatment with developed formulation was more efficacious since it was coformulated with GTE, which acts as an adjuvant for the management of inflammatory disease like asthma. CONCLUSION It is contemplated that, use of GTE as an adjuvant to anti leukotriene drug played a significant role in asthma management by reducing oxidant injury. Since, studies in animals do not directly translate to human biology, further multi-control studies with better sampled patient population and more number of patients are needed.