The present study investigated the effect of co-grinding raloxifene HCL (RHCL) with different superdisintegrants, namely crospovidone (CP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), using a ball mill, in order to determine the potential effect on dissolution rate and bioavailability of raloxifene hydrochloride (RHCL). The dissolution studies of the co-ground compositions and the corresponding physical mixtures were carried out in U.S. Pharmacopeia (USP) Type II apparatus. The solid state interactions of the co-ground and the physical mixtures were evaluated by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The pharmacokinetics of co-ground mixture (1 : 5 RHCL : CP) and milled RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague-Dawley rats. DSC studies showed that the crystalline nature of RHCL was reduced after co-grinding with superdisintegrants, while co-grinding with CP resulted in significant particle-size reduction of the mixture. Significant enhancement in dissolution rate was observed with coground mixture of RHCL with CP (1 : 5). The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with co-ground mixture of RHCL, CP (1 : 5) compared to animals treated with milled RHCL. Co-grinding of RHCL with CP, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability.

EFV is a non-nucleoside reverse transcriptase inhibitor and is used as part of the highly active antiretroviral therapy for the treatment of human immunodeficiency virus type 1 (HIV) infection. It is also used in combination with other antiretroviral agents as part of an expanded post-exposure prophylaxis regimen to prevent HIV transmission for those exposed to materials associated with a high risk of HIV transmission.EFV has poor aqueous solubility and is a BCS class II drug (1). EFV tablets of 600 mg are available, while lower doses (50, 100 and 200 mg) are generally available as capsules and are prepared by a wet granulation process (2, 3). 185Acta Pharm. 60 (2010) [185][186][187][188][189][190][191][192][193][194][195] Original research paper DOI: 10.2478/v10007-010-0019-6 Impact of superdisintegrants on efavirenz release from tablet formulations Efavirenz (EFV) tablets of different doses were prepared by a wet granulation process using different superdisintegrants such as crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP) to evaluate the role of different disintegrants on the in vitro release of EFV. Further, the mode of addition of disintegrants on EFV dissolution from tablets containing 600 mg of the drug was evaluated by incorporating the disintegrants extragranularly (EG), intragranularly (IG) or distributing them equally (IG and EG). In vitro dissolution of the prepared tablets was conducted using the recommended medium and a dissolution medium developed in-house, which had the ability to discriminate between the formulations.The t 50 and t 80 values were indicative of the fact that the drug release was faster from tablet formulations containing CP. CP was able to release the drug faster than the other two disintegrants in both dissolution media and the drug release was unaffected by the mode of CP addition.Keywords: efavirenz, superdisintegrants, granulation * Correspondence; e-mail: rajeshyelchuri@rediffmail.com Brought to you by | MIT Libraries Authenticated Download Date | 5/12/18 2:48 PM Superdisintegrants generally improve disintegration efficiency compared to traditional disintegrants. They are generally used at low levels in solid dosage forms, typically 1-10 % of mass relative to the total mass of the dosage unit (4). Examples of superdisintegrants are crosscarmellose sodium (CCS), sodium starch glycollate (SSG) and crosspovidone (CP), which are cross-linked cellulose, a cross-linked starch and a cross--linked polymer (polyvinyl pyrrolidone), respectively. Wet granulation is one of the frequently used techniques to prepare blends to be compressed into tablets. The disintegrant can be incorporated in the blend before granulation, referred to as intragranular addition (IG), or after granulation, referred to as extragranular addition (EG), or it can be distributed both intra and extragranularly. EXPERIMENTAL MaterialsEfavirenz (Aurbindo Pharma Ltd., India) was purchased from the source indicated. Crosscarmellose sodium (Ac-di-sol ® , FMC biopolymer) and SS...

No abstract

ABSTRACT