ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation

DEVELOPMENT AND VALIDATION OF NEW SIMPLE, SENSITIVE AND VALIDATED UV-SPECTROPHOTOMETRIC AND RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF PARACETAMOL AND ETODOLAC IN MARKETED FORMULATION

A simple, precise and highly selective analytical method was developed for simultaneous estimation of Paracetamol and Etodolac in tablet formulation. Estimation was carried out by multicomponent mode of analysis at selected wavelength of 256 and 286 nm for Paracetamol (PCM) and Etodolac (ETD) respectively in methanol: water (60:40). The method was validated in terms of linearity, accuracy (% Recovery), Precision (Interday, intraday, and reproducibility) and robustness. Both methods were linear (R2 = 0.997- 0.999 for UV method and 0.998 for RPLC method) and accurate (% recovery was 98.39-101.17%). The method was also obtained precise (% RSD <2 %) and robust. The linearity was obtained in the concentration ranges of 5.25 μg/ml for paracetamol and 3-16 μg/ml for Etodolac. The method was validated as per international conference of Harmonization (ICH) guidelines. Keywords: Paracetamol, Etodolac, UV, RP-HPLC, ICHÂ

FORMULATION AND EVALUATION OF MEDICATED CHEWING GUM OF DOLASETRON AS AN ANTIEMETIC AGENT

An attempt has been made to formulate new chewing gum for Dolasetron. The new drug delivery system was obtained, at room temperature conventional pharmaceutical equipment. The resulting chewing gum comprises a gum core combined with fillers, antioxidants, coloring agent and plasticizers, which provide smooth appearance and flexibility during storage and chewing. Drug release from a dosage form is the critical step in drug absorption and bioavailability, thus an experimental work has been designed to evaluate the efficiency of this kind of therapeutic system by verifying its capability to release the drug dose and by assessing the delivery of Dolasetron for bypassing the hepatic first pass effect. Simple diffusion into the medium causes the release of only a small percentage of the drug contained in the medicated chewing gum, while the delivery of the major part of the dose occurs during mastication. In the present study, an attempt has been made to formulate the chewing gum of Dolasetron. Different formulations of chewing gum with varying concentration of plasticizers like glycerol and castor oil were formulated. MCG II formulation was considered to be the best-optimized formula which consists of synthetic gum base (45%), Sorbitol (14.6%), sucrose (46%) etc. which shows first slow release the fast release in the phosphate buffer saline (ph 6.8). The cumulative drug release of MCG II formulation was found to be 99.43 %. From this study, we can conclude that the medicated chewing formulation can be a better choice in the coming years which provides several benefits and also benefits commercially.Â