Research Article SOLID STATE MODIFICATION FOR THE ENHANCEMENT OF SOLUBILITY OF POORLY SOLUBLE DRUG: CARRAGEENAN AS CARRIER VEDHA HARI B.N. * , YASMIN BEGUM A., RAMYA DEVI D. Department of Pharmaceutical Technology, SCBT, SASTRA University, Thanjavur- 613401. Tamil Nadu, India. Email: vedhahari@scbt.sastra.edu Received: 30 July2010, Revised and Accepted: 05 Oct 2010 ABSTRACT The aim of the work was to evaluate the effect of carrageenan on the solubility of poorly soluble, BCS class II, NNRTI drug Efaverinz for its solubility enhancement. Solid dispersions were formulated using naturally obtained polysaccharide carrageenan in the molecular ratio of 1:1, 1:3, 1:5 using trituration method (TM), solvent evaporation method (SE) and kneading method (KM). The formulated solid dispersions were manually filled in hard gelatin capsules (size 1) and evaluated for the physicochemical properties like weight variation (100-300 mg), disintegration time (3-4 min), drug content (99-103 %) and dissolution using water and compendial media water with 1% sodium lauryl sulphate. The solid dispersions were subjected to instrumental analysis for checking its purity using fourier transform infra red spectroscopy (FTIR) and polymorphic changes using differential scanning calorimetry (DSC). The obtained data confirmed the enhancement of the solubility of Efavarinz using carrageenan by two folds. Keywords: Solid dispersions, Carrageenan, Hot stage microscopy, HIV, Anti-retroviral Therapy (ART) INTRODUCTION Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRIT) and is used as a part of highly active anti retroviral therapy (HAART) for the treatment of Human Immuno deficiency Virus (HIV) type I. Efavirenz was approved by the Food and Drug Administration (FDA) on September 21, 1998 making it the 14 th approved antiretroviral drug. It is also used in combination with other anti retroviral agents like reverse transcriptase inhibitors (RTI). The symptomatic IUPAC name is 8-chloro 5-(2-cyclo propyl ethynyl) 5-trifluoro methyl 4-oxa 2- aza tri cyclo (4.4.0) deca 7,9,11 trien 3-one. The molecular formula and molecular weight of the drug is C14H9ClF3NO2 and 315.6 g/mol respectively. The drug-protein binding and its bioavailability are reported in the range of 99.5% - 99.75% and 42% approximately 1 . Efavirenz is practically insoluble in water (<10mcg/ml) and so it is categorized under BCS class-II. Efavirenz has been used as a first line treatment for AIDS in preference to the protease inhibitor. The natural carrageenan is isolated from the species of red seaweed, family of rhodophyceae. The major sources are the chondrus crispus, eucheuma spinosum and eucheuma cottonii. The former is usually found in cold climate territories and the other two are generally grown in temperature climate. It is made as high molecular weight linear polysaccharide comprising of galactose, sulfated and non-sulfated joined by α-(1-)- and β-(1-4) glycosidic linkage 2 . Carrageenan acts as thickening, suspending and gelling agent for many industrial applications. There are three types of carrageenan such as kappa, lota and lambda which indicates the addition of potassium, calcium and sulfate molecules respectively. Solutions of carrageenan are more stable in slight acidic, neutral and alkaline conditions, and in water it forms a weak gel at very low concentrations. It also allows solids to remain suspended in solution. General applications of carrageenan includes drug delivery systems for both oral and topical routes, wound dressing, cosmetics, contraceptive gels, dentrifices and in humidity control as well as in biotechnology for cell immobilization 3 . MATERIALS AND METHODS Materials Efavirenz obtained as gift sample from ISP Hong Kong (P) Ltd., Hyderabad, India. Carrageenan procured from Himedia Lab (P) Ltd., Mumbai, India. Sodium lauryl sulphate was purchased from S.D Fine chemicals Ltd., Mumbai, India. All other reagents were of analytical grade. Preparation of solid dispersion In the molar ratios of 1:1, 1:3, 1:5 of drug to carrier (carrageenan), the solid dispersions of Efavirenz were prepared by using the well established techniques (Table 1). Trituration method For the preparation of physical mixture, the previously sieved and weighed Efavirenz and carrageenan was taken and homogeneously blended in a mortar and pestle. The physical mixtures were stored in desiccators with anhydrous CaCl2 at ambient temperature until used, to prevent the moisture absorption and contamination 4,5 . Solvent evaporation method The requisite amount of Efavirenz and carrageenan carrier was dissolved in easily evaporating organic solvent such as methanol and allowed to stand overnight. The so formed solid dispersions were subjected for complete dryness at 60 o C, the solvent was removed under vacuum condition until it became dry. The pulverized dried mass was passed through 44-mesh sieve and stored in desiccators for future use. Kneading Method The Efavirenz and complexing carrier were accurately weighed in different drug-polymer ratio 1:1, 1:3, 1:5 and transferred to mortar for kneading (31) using hot water up to 45 minutes. Sufficient hot water was added to maintain paste like consistency. The resulting paste was then dried in hot air oven at 45ºC for 24 hours. The dried dispersions were milled and passed through sieve no. 18. The prepared dispersions were stored in amber coloured glass vials and used for further studies 4 . Filling in Capsules The formulated solid dispersion was accurately weighed for its equivalent weight as per the yield and filled in hard empty gelatin capsule shells by manual pour filling method. The filled capsules were utilized for the further studies. Characterization of Solid dispersion FT-IR Spectroscopy KBr pellet technique was used to determine the compatibility between drug and polymer. The modified procedure of Fourier Transform Infra-Red Spectrophotometer (Perkin- Elmer system 200 FT-IR spectrophotometer) was used for the measurement of pure drug, polymer and drug-loaded solid dispersion formulation spectrums. The pellets were prepared on KBr-press under hydraulic                               International Journal of Applied Pharmaceutics       