Purpose Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression. Methods Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats. Results The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs' activation to a lesser extent. Conclusion The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.

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Zein/Phospholipid Composite Nanoparticles for Successful Delivery of Gallic Acid into aHSCs: Influence of Size, Surface Charge, and Vitamin A Coupling

Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression. GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored. Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats’ livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers’ expressions and elevated HSCs’ apoptosis. These findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.

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Impact of Reverse Micelle Loaded Lipid Nanocapsules on the Delivery of Gallic Acid into Activated Hepatic Stellate Cells: A Promising Therapeutic Approach for Hepatic Fibrosis

The aim of the present study was to develop sustained release formulation of Isoniazide to maintain constant therapeutic levels of the drug for over 12 hrs. Various polymers such as Guar gum, HPMCK100 M, PEG 6000 and Carbopol 934 p were employed as polymers. Isoniazide dose was fixed as 100 mg. Total weight of the tablet was considered as 400 mg. Polymers were used in the concentration of 100, 150 and 200 mg. All the formulations passed various physicochemical evaluation parameters and they were found to be within limits. Whereas from the dissolution studies it was evident that the formulation (F6) showed better and desired drug release pattern i.e.,96.10 % in 12 hours. It followed zero order release kinetics.

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Formulation of Isoniazide Sustained Release Formulation by Using Carbopol 934 P

Embelin, a naturally occurring benzoquinone, is obtained from fruits of Embelia tsjeriam cottam, which plays a vital role in the Ayurvedic system of medicine. An approach for the stress degradation was successfully applied for the development of stability indicating HPTLC method for the determination of Embelin. It was spotted on the plates precoated with silica gel 60 F254 and developed using toluene: ethyl acetate: formic acid, (6:3.5:0.5 v/v/v) as mobile phase. Densitometry analysis was carried out at 291 nm. The method showed high sensitivity with good linearity over the concentration range of 200-1000ng/spot with correlation coefficient value 0.997. The accuracy of the method was established based on the recovery studies. The LOD and LOQ were 6.09ng/band and 18.48ng/band respectively. The system showed a peak for Embelin at Rf of 0.68 ± 0.02.The aim of our study was to observe the effect of various stress conditions on this potential drug candidate. Stress testing of Embelin was carried out according to the International Conference of Harmonization (ICH) guideline Q1A (R2). Embelin was subjected to stress conditions of acid, alkaline hydrolysis, oxidation, photolysis and thermal degradation. A significant degradation was found to occur by acid and oxidation hydrolysis and to a lesser extent under thermal stress and alkaline hydrolysis; and much lesser with photolytic stress. Stress degradation studies on embelin provide an insight into its stability.

Development and validation of stability indicating hptlc method for estimation of embelin in embelia tsjeriam cottam

The objective of the present study was to develop a sustained release matrix tablets of Losartan potassium, an anti hypertensive drug. The sustained release tablets were prepared by wet granulation and formulated using different drug and polymer ratios. Hydrophilic natural polymers like xanthan Gum (XG), guar gum and cellulose were used. Compatibility of the drug with various excipients was studied. The compressed tablets were evaluated and showed compliance with Pharmacopoeial limits. Formulation was optimized (F2) on the basis of acceptable tablet properties and in vitro drug release. The resulting formulation produced matrix tablets with optimum hardness, consistent weight uniformity and friability. All tablets but one exhibited gradual and near completion sustained release for losartan potassium and 90.88% released at the end of 12h. The results of dissolution studies indicated that formulation F2 (drug to polymer 1:2) is the most successful of the study and exhibited drug release pattern very close to theoretical release profile. A decrease in release kinetics of the drug was observed on increasing polymer ratio. Applying exponential equation, all the formulation tablets (except F2) showed diffusion-dominated drug release. The mechanism of drug release from F2 was diffusion coupled with erosion.

https://sierrajournals.com/index.php/IJAPSR/article/download/980/628

Development and Evaluation of Sustained Release Matrix Tablets of Losartan potassium

Objectives: A new simple spectrophotometric method for simultaneous estimation of Embelin and Gallic Acid in Vidang, Harade and Vidangadi Churna was investigated. The λmax of Embelin and Gallic Acid were found to be 341 and 258 nm. Method: The graphical absorbance ratio method was used for simultaneous estimation of Embelin and Gallic acid in Vidangadi Churna, and the Isoabsorbtive point for simultaneous estimation of both the drug were found to be 307.5 nm. The method obeys Beers law in the concentration range from 2-12 μg/ml. The correlation coefficient was found to be 0.9973 for Embelin and 0.998 for Gallic Acid. The method was validated as per ICH guidelines. Results: The result of estimation of Embelin in Vidang, Gallic acid in Harade and both in Vidangadi Churna were found to be 1.05 percent, 1.04 percent, and 1.85. The proposed method was validated for linearity, accuracy and application for assay as per ICH guidelines. Conclusion: The study showed good reproducibility and recovery with percent RSD less than 2. So, the proposed method was found to be simple, specific, precise, and accurate. Hence it can be applied for simultaneous estimation of Embelin and Gallic Acid in various Ayurvedic Churna formulations. Key Word : Embelin, Vidang. Gallic Acid, Harade, Vidangadi Churna.

Standardization, development and validation of spectrophotometric method for simultaneous estimation of embelin and gallic acid as individual and in combination in ayurvedic churna formulation

Formulation of time dependent sustained release tablet of nimodipine and its evaluation using linear regression analysis

Standardization, development and validation of spectrophotometric method for estimation of piperine in ayurvedic vati formulation

Floating tablets of Marichyadi Vati were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using HPMC E50 LV act as Matrixing agent, Carbopol as floating enhancer, microcrystalline cellulose as binder, Sodium bi carbonate as effervescent agent with other excipients. The simplex lattice design was used for selection of variables for tablets formulation. Formulation was optimized on the basis of floating time and in vitro drug release. The results showed that the floating lag time for optimized formulation was found to be 61 second with about 97.32 % of total drug release within 3 hours. The vitro release profiles of drug from the formulation could be best expressed zero order with highest linearity r = 0.9943. It was concluded that the gastroretentive drug delivery system can be developed for Marichyadi Vati containing Piperine to increase the residence time of the drug in the stomach and thereby increasing bioavailability. Keywords—Piperine, Marichyadi Vati, Gastroretentive drug delivery, Floating tablet.

Imran Khan Pathan

Papers

Standardization, development and validation of spectrophotometric method for simultaneous estimation of embelin and gallic acid as individual and in combination in ayurvedic churna formulation

Formulation of time dependent sustained release tablet of nimodipine and its evaluation using linear regression analysis

Standardization, development and validation of spectrophotometric method for estimation of piperine in ayurvedic vati formulation

Development and Evaluation of Gastro Retentive Floating Tablets of Ayurvedic Vati Formulation