Comparative Dissolution Studies for Mefenamic Acid-Polyethylene Glycol Solid Dispersion Systems and Tablets

Abstract

The purpose of this study was to enhance the dissolution of mefenamic acid (MFA) through the formation of solid dispersion systems, and to compare the dissolution of the unformulated dispersions with those of formulated dispersions in tablets. Solid dispersions of MFA were prepared in polyethylene glycol 3350 (PEG) as a binary system, and PEG and Tween 20 (TW) as a ternary system by the melt method. The dispersions were characterized by dissolution, scanning electron microscopy, and powder x-ray diffraction studies. A decrease in MFA composition in the binary dispersion systems from 50 to 5% w/w resulted in a 50% increase in the dissolution rate during the period of study, and this was threefold higher than that of pure MFA. Incorporation of TW in the preparation of ternary dispersion systems resulted in a further increase in MFA dissolution. A sevenfold increase in MFA dissolution was observed when the ternary system composition was MFA/PEG/TW 4.7:93:2.3 (% w/w). Scanning electron microscopy and x-ray diffraction pictures showed an increase in size and decrease in crystallinity of the dispersions, respectively. Compression of the dispersions into tablets did not have any effect on the dissolution of the drug from the dispersions. Compression of pure MFA and Avicel PH 101, which was used as a diluent and disintegrant, resulted in a threefold increase in dissolution. However, the dissolution of the uncompressed mixture was identical to that of pure MFA. Thus, further processing of the solid dispersions into tablets did not decrease the rate of dissolution of the drug in the dispersions. This may be very important in the formulation of solid dispersions as tablets, which could lead to a reduction in the dose of practically water-insoluble drugs.

Applicability of sucrose laurate as surfactant in solid dispersions prepared by melt technology

“…Water-soluble carriers such as high-molecularweight polyethylene glycols (PEGs) and polyvinylpyrrolidones (PVPs) have been most commonly used for solid dispersions (Bikiaris et al, 2005;Craig and Newton, 1991;Leuner and Dressman, 2000;Saharan et al, 2009;Serajuddin, 1999). The use of surfactants with solubilizing properties, such as polysorbates, poloxamers, Gelucires (polyethylene glycol glycerides), sodium lauryl sulfate or vitamin E TPGS have also attracted considerable interest recently (Dehghan and Jafar, 2006;Jagdale et al, 2010;Liu and Wang, 2007;Mura et al, 1999;Okonogi and Puttipipatkhachorn, 2006;Owusu-Ababio et al, 1998;Sethia and Squillante, 2002;Vasconcelos et al, 2007). As described in the review by Vasconcelos et al (2007), the third-generation solid dispersion systems contain a surfactant carrier, or a mixture of amorphous polymers and surfactants as carriers.…”

Dissolution improvement of high drug-loaded solid dispersion

“…1,2 An obstacle of solid dispersion technology in pharmaceutical product development is that a large amount of carrier, ie, more than 50% to 80% wt/wt, was required to achieve the desired dissolution. [3][4][5] This high percentage of carrier causes consistency of product performance at the time of manufacturing. This is a major consideration in that the number of market products arising from this approach has been less than expected.…”

Development and in Vitro Evaluation of Ibuprofen Mouth Dissolving Tablets Using Solid Dispersion Technique

“…This is a major consideration in that the number of market products arising from this approach has been less than expected. [6][7][8][9] With regard to carriers for SD formulations, many carriers such as polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose, hydroxypropyl methylcellulose phthalate (HPMCP), Gelucires ® , Eudragits ® and chitosans have been reported to improve the solubility and bioavailability of poorly water soluble drugs. [10][11][12] Among the various carriers used in the formation of SD, PEG is most commonly used.…”