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.
The effects of selected superdisintegrants on the dissolution behavior of several cationic drugs with varying water solubility were evaluated. All formulations were made with fixed disintegrant concentration and equal drug load using a model formulation. Tablets were made by direct compression and were compressed to equal hardness. Dissolution studies were carried out in dissolution media specified in the compendium (USP) or in media recommended by the U.S. Food and Drug Administration (FDA) for the respective actives. The effect of media pH on the dissolution of drugs was also evaluated.The use of crospovidone significantly improved the dissolution of the cationic drugs in the model formulation when compared with the other superdisintegrants studied. The compendial or the FDA recommended media, in most cases, was able to discriminate among the tablets containing different superdisintegrants.Crospovidone can be effectively used as a tablet disintegrant to improve the dissolution of either soluble or poorly soluble cationic drugs.
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...
Raloxifene HCl (RHCl) is known to be susceptible to oxidation and forms the corresponding N-oxide derivative as the primary degradation product. The purpose of this study was to evaluate the role of excipients on the generation of the N-oxide derivative from the corresponding RHCl-excipient binary mixtures. Binary mixtures of RHCl with crospovidone, povidone, magnesium stearate, Tween 80 and anhydrous lactose in drug: excipients ratio of 1 : 1 (crospovidone and povidone); 10 : 1 (Tween 80 and magnesium stearate) and 1 : 5 (anhydrous lactose) were prepared by both dry blending (trituration) and wet blending (to improve contact between drug and excipients). The prepared binary mixtures were then stored at 25, 40, 75 and 125°C and generation of the N-oxide derivative was monitored over six months using a validated HPLC method. Pure drug and excipients stored similarly acted as controls. Further, all the individual excipients (used as control) were monitored for peroxide impurity generation using an in-house colorimetric method. The results showed that N-oxide generation was observed from all binary mixtures and the amount of N-oxide derivative formed were always higher from the mixtures prepared by wet blending and the amount of N-oxide derivative formed was dependent on storage temperature. This study thus shows that the presence of peroxide in the excipient and its role in oxidative degradation of drug substance calls for monitoring of the peroxide impurity present in the excipients used for formulating of drug sensitive to oxidation as used herein.Key words raloxifene HCl; excipient; N-oxide-raloxifene; povidone; crospovidone Incompatibility between drugs and excipients can alter the stability and bioavailability of drugs, thus affecting its safety and efficacy. Study of drug-excipient compatibility is an important and integral process in the development of a stable dosage form. Many reports are available in the literature that has deliberated the importance of this issue and various methods of compatability testing have been discussed. [1][2][3][4][5] Raloxifene HCl (RHCl), is a selective estrogen receptor modulator shown to be effective in the prevention of osteoporosis, 6) which could be a potential substitute for long-term female hormone replacement therapy. Raloxifene is available as 60 mg tablet under the brand of Evista (Eli-Lilly) and contains 12.5% w/w RHCl, 5% povidone, 6% crospovidone and a combination of other excipients including anhydrous lactose, lactose monohydrate, Tween 80 and magnesium stearate. In an earlier published report, 7) it was disclosed that raloxifene forms a N-oxide derivative as a degradation product when the tablets were stored in sealed bottles and open containers at both 30°C/60% relative humidity (RH) and at 40°C/75% RH. Stability studies on binary mixtures of RHCl with primary excipients used in the tablet (Evista) were reported, 7) wherein the binary mixtures were stored at 125°C for a period of 31 d. The results showed that maximum amount of N-oxide derivative generation we...
The aim of the min present study was to develop pantoprazole suspension containing delayed release (DR) microspheres to target the drug release intestine. This study is divided into two sections, first one is to prepare DR pantoprazole microspheres and second is to formulate into reconstitutional oral suspension. Quality by Design (QbD) approach was used in the study. Polymethacrylate (Eudragit L100-55) was used for the development of delayed release microspheres. To prepare reconstitutional suspension formulation, 90% particle size of microspheres less than 50 microns and with 90% loading efficiency was used. Xanthan gum is used as suspending agent and D-mannitol is used as sweetening agent. FTIR study shows compatibility of the drug with polymer. Moreover, the same release rate of pantoprazole from the suspension and microspheres alone indicated that the suspension medium studied did not affect the property of drug release during storage.
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