Formulation and Evaluation of Gastro Retentive Mucoadhesive Sustained Release Pellets of Acyclovir

Acyclovir is an antiviral drug, belonging to the deoxyguanosine family, widely prescribed for the treatment of herpes simplex viral infections, as well as in the treatment of herpes zoster (shingles). Oral bioavailability of acyclovir is very low (10–20%) owing to its first pass metabolism with elimination half-life (t1/2) of 2-3 h. It has absorption window in upper gastrointestinal tract. Due to its rapid elimination from site of absorption and short biological half life, sustained release formulation system for acyclovir is advantageous. In this study, gastro retentive muco-adhesive SR pellets of acyclovir was prepared using HPMC K 100M as matrix former and Sodium CMC as mucoadhesive polymer by extrusion spheronization technique. Acyclovir pellets prepared with higher concentration of HPMC (batch G) showed in vitro drug release for 12 h with sufficient mucoadhesion strength and ex vivo resident time. Release kinetic studies indicated that drug release data had best fit to Higuchi’s model. In-vivo studies in rat model proved that relative bioavailability of acyclovir SR pellets get increased by 1.98 fold as compared plain drug suspension. The optimized formulation batch G was found to be stable during six months accelerated stability period

Optimization of process variables for phyllanthin extraction from Phyllanthus amarus leaves by supercritical fluid using a Box-Behnken experimental design followed by HPLC identification

The response surface methodology using the Box-Behnken design was established to describe supercritical carbon dioxide assisted extraction of phyllanthin from Phyllanthus amarus Schum and Thonn leaves prior to HPLC analysis. The effects of extraction pressure, temperature, modifier concentration and extraction time on the yield of phyllanthin were investigated. By solving the regression equation, the optimum conditions were as follows: extraction pressure 23.2 MPa, temperature 40 °C, methanol as modifier at a concentration 10 % and time 90 min. Under these conditions, the phyllanthin yield was 12.83 ± 0.28 mg g-1, which was in good agreement with the predicted values. Modifier concentration and extraction time showed a significant effect on the phyllanthin yield

Formulation and Evaluation of Gastro Retentive Mucoadhesive Sustained Release Pellets of Acyclovir

Acyclovir is an antiviral drug, belonging to the deoxyguanosine family, widely prescribed for the treatment of herpes simplex viral infections, as well as in the treatment of herpes zoster (shingles). Oral bioavailability of acyclovir is very low (10–20%) owing to its first pass metabolism with elimination half-life (t1/2) of 2-3 h. It has absorption window in upper gastrointestinal tract. Due to its rapid elimination from site of absorption and short biological half life, sustained release formulation system for acyclovir is advantageous. In this study, gastro retentive muco-adhesive SR pellets of acyclovir was prepared using HPMC K 100M as matrix former and Sodium CMC as mucoadhesive polymer by extrusion spheronization technique. Acyclovir pellets prepared with higher concentration of HPMC (batch G) showed in vitro drug release for 12 h with sufficient mucoadhesion strength and ex vivo resident time. Release kinetic studies indicated that drug release data had best fit to Higuchi’s model. In-vivo studies in rat model proved that relative bioavailability of acyclovir SR pellets get increased by 1.98 fold as compared plain drug suspension. The optimized formulation batch G was found to be stable during six months accelerated stability period

Optimization of supercritical fluid extraction and HPLC identification of wedelolactone from Wedelia calendulacea by orthogonal array design

The purpose of this work is to provide a complete study of the influence of operational parameters of the supercritical carbon dioxide assisted extraction (SC CO2E) on yield of wedelolactone from Wedelia calendulacea Less., and to find an optimal combination of factors that maximize the wedelolactone yield. In order to determine the optimal combination of the four factors viz. operating pressure, temperature, modifier concentration and extraction time, a Taguchi experimental design approach was used: four variables (three levels) in L9 orthogonal array. Wedelolactone content was determined using validated HPLC methodology. Optimum extraction conditions were found to be as follows: extraction pressure, 25 MPa; temperature, 40 °C; modifier concentration, 10% and extraction time, 90 min. Optimum extraction conditions demonstrated wedelolactone yield of 8.01 ± 0.34 mg/100 g W. calendulacea Less. Pressure, temperature and time showed significant (p < 0.05) effect on the wedelolactone yield. The supercritical carbon dioxide extraction showed higher selectivity than the conventional Soxhlet assisted extraction method

Potential herb-drug interaction of a flavone glycoside from <em>Cuminum cyminum</em>: Possible pathway for bioenhancement of rifampicin

776-782Traditional knowledge on classical herbal based Ayurvedic formulation namely ‘Trikatu’ in the Indian system of medicine has led to the discovery of ‘Risorine’, a world’s first boosted rifampicin in combination with piperine (one of ingredient in Trikatu) as bioenhancer for the treatment of tuberculosis. This encourages us to combine rifampicin with a flavone glycoside (CC-I), one of ingredient of Cuminum cyminum which found its application in culinary purposes and immensely widespread in diverse ethnomedical systems worldwide as an integral part of folklore therapy. Therefore, aim of the study is to explore the reason for bioenhancement of rifampicin by CC-I using a panel of in vitro and in vivo experimentations for the first time. Plasma concentration of rifampicin was markedly enhanced by CC-I orally in Wistar rats. Mechanistic studies showed that CC-I have action on efflux transporters based on rhodamine transport and P-glycoprotein dependent ATPase assay but no alteration of in vitro transcellular diffusion and plasma protein binding of rifampicin. Intestinal transit of rat was not affected upon treatment with CC-I whereas inhibition of CYP3A4 in rat and human liver microsomes was occurred to a little extent. Bioenhancer effect of CC-I was mainly through improving absorption by down regulation of efflux transporters

Development and Validation of a RP-HPLC Method for the Simultaneous Determination of Rifampicin and a Flavonoid Glycoside - A Novel Bioavailability Enhancer of Rifampicin

Purpose: To develop and validate a sensitive HPLC method for the separation and simultaneous estimation of two ingredients in a composition comprising of rifampicin and a flavonoid glycoside (an enhancer of oral bioavailability of rifampicin). Methods: Reverse phase (RP) chromatographic separation and estimation was achieved using a Shimadzu HPLC system. RP-18 column was used at the following optimised conditions: mobile phase, acetonitrile:phosphate buffer, 50 mM, pH 5.0 in a ratio of 60:40 v/v; oven temperature, 40 °C; flow rate, 0.8 ml min-1; detection wavelength, 340 nm; and total run time, 15 min. Results: The developed method was validated in terms of linearity, range, accuracy, precision, limit of detection, limit of quantification, robustness and specificity. Good linearity was observed (r2 > 0.999) over the study range of both ingredients. The precision values for rifampicin and the flavonoid glycoside were in the range 1.08-2.77 and 1.14-2.98 %, respectively, while the limit of quantification was 0.10 and 0.05μg mL-1 respectively. The method was found to be robust and specific for both ingredients. Conclusion: The developed method has a potential application in preclinical and clinical studies