Preparation,In vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac

Abstract

The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.

Design and evaluation of Carvedilol nanocrystals sustained release tablets

“…Samples were compressed with potassium bromide and scanned between 4000-400 cm -1 in FT-IR (Analytical 2500, Germany). The change in spectra of the drug in the presence of excipients was investigated to identify the interaction of drug molecule with the excipients if any (Mutalik et al, 2007).…”

Modulating drug release profiles by lipid semi solid matrix formulations for BCS class II drug – anin vitroand anin vivostudy

“…This difference in the release was due to the pH-dependent solubility of the drug (Manjanna et al, 2009). A pH 6.8 buffer was hence selected as a dissolution media for preliminary screening and selection of immediate release SSM formulation, as recommended by Mutalik et al (2007) for aceclofenac. Dissolution data for various SSM bases studied are presented in Table 1 and Figures 2 and 3.…”

“…In order to obtain preliminary data for justifying sustained release claim, in vivo studies were also performed on S13 formulation, using carrageenan-induced rat paw edema model. Many authors have successfully used this acute model of inflammation for evaluating sustained release formulations (Arora & Mukherjee, 2002;Panusa et al, 2011). Sustained release SSM formulation, S13, also gave maximum edema inhibition of 81 ± 8% at 3 h, which was statistically significant at p50.01 when compared to plain drug.…”

A Comparative Study of the Pharmacokinetics of Conventional and Sustained-release Tablet Formulations of Aceclofenac in Healthy Male Subjects

“…properties of the formulated tablets Tablet thickness was in the range 3.6 -3.9 mm; diameter, 11.0mm; and hardness, 5.0 -8.0 g/cm 2 . Tablet friability and coefficient of weight variation (for individual tablets) were 0.5 and 1.4 to 3.5 %, respectively.…”

“…The drug demonstrates better gastric tolerance than other non steroid anti-inflammatory drugs (NSAIDs) such as indomethacin and diclofenac [2]. Its recommended dose is 100 mg twice a day orally in the form of tablets.…”