FORMULATION AND CHARACTERIZATION OF HPMC AND HPMCAS BASED SOLID DISPERSIONS OF FENOFIBRATE: A COMPARATIVE STUDY Original Article ANKIT RAMPAL, MANMEET SINGH, SHANTA MAHAJAN, NEENA BEDI Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India (143005) Email: neena.pharma@gndu.ac.in * Received: 16 Feb 2019, Revised and Accepted: 11 Apr 2019 ABSTRACT Objective: The aim of the present study was to investigate the effect of novel polymeric carriers and to develop solid dispersion formulation that could improve in vitro profile of Fenofibrate (FB). Methods: Spray drying technique was used to fabricate solid dispersions with hydrophilic carriers, mainly hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS). Solid dispersions in the form of spray-dried powder were characterized with respect to the pure drug and the corresponding physical mixtures by optical microscopy, x-ray diffraction (XRD), fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). Size and morphology of optimized solid dispersion were performed by scanning electron microscopy (SEM). Furthermore, in vitro dissolution comparisons were carried out between the optimized solid dispersion against the pure drug and the physical mixtures. Results: Solubility studies demonstrated that the solubility of FB was not affected by pH change. The transformation of crystalline FB into an amorphous solid dispersion powder has been clearly demonstrated by optical microscopy. The molecular dispersion of drug in the dispersion matrix prepared by spray drying was confirmed in XRD and DSC studies. IR spectroscopy was observed with negligible incompatibility of the drug with polymers. Spherical morphology was observed in SEM with no evidence of FB crystals. The prepared solid dispersions exhibited dissolution improvement as compared to the pure drug and spray dried FB in 0.05 M SLS, with HPMCAS as the superior carrier over HPMC. Conclusion: The present study vouches better in vitro profile of FB from spray-dried HPMCAS based solid dispersions. Keywords: Solubility, HPMC, HPMCAS, Solid dispersions, Crystallinity © 2019 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open-access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2019v11i4.32592 INTRODUCTION About 40% of New Chemical Entities in drug development pipelines suffered from poor water solubility or dissolution rate-limited absorption which eventually falls into the Biopharmaceutics Classification System (BCS) Class II and thus they fail to reach the market. These poorly water-soluble drugs are associated with slow drug absorption leading to inadequate and variable bioavailability and gastrointestinal mucosal toxicity [1]. Techniques have been developed to address the low aqueous solubility challenges, including chemical modification, such as pro-drugs and salt formation, or formulation methods such as particle size reduction, co-crystal formation, inclusion complexes using cyclodextrins and lipid formulations and solid form changes such as nanocrystals and amorphous dispersions of API and polymers [2]. Of these techniques, amorphous solid dispersion is a useful approach to increase the dissolution rate of poorly water-soluble drugs and thereby improve their bioavailability, although this must be proved for each drug. The preparation of the solid dispersion involves drug deposition on the surface of an inert carrier which results in a greater surface area of the drug leading to a faster rate of dissolution [3]. Recently used methods for the preparation of amorphous solid dispersions include mechanical grinding, melting, hot melt extrusion, spray drying, lyophilization and supercritical fluid precipitation [4]. Spray drying is one of the effective methods for preparing amorphous solid dispersion which consists of suspending the drug and the polymer in a common solvent and then drying it to form uniform nanoparticulate size powder [5]. The scalability and efficient critical process parameters of spray drying technology based solid dispersions are widely applied in the pharmaceutical industry, which provides equalized content uniformity and nanosized distributed solid surfaces. FB, a prodrug of fenofibric acid, is used for the treatment of hypertriglyceridemia, mixed dyslipidemia, and hyper- cholesterolemia, as it can reduce levels of triglycerides, total cholesterol and low-density lipoprotein [6]. However, FB is a neutral lipophilic drug (log P = 5.2), which is practically insoluble in water. It is classified as a class II BCS drug and oral bioavailability of approximately 30% is reported in humans. Many nanoformulations like mesoporous solid particles, liposomes or tablet approaches have been studied to improve the solubility of FB. However, the majority of these formulations used either a special matrix of mesoporous surfaces, superdisintegrants or surfactants as modified excipients lacking long-term biocompatibility or involved technically challenging processes. Some reports have confirmed that silica can act as an immunogenic sensitizer and induce contact hypersensitivity. Furthermore, the formulation must be carefully designed because the pore architecture of silica may greatly influence its biocompatibility, and high dose and long-term usage should be avoided [5, 6]. The spray drying technique used for the preparation of the solid dispersion using different hydrophilic polymers such as HPMC and HPMCAS has not been explored to improve the aqueous solubility of FB. In the present study, an attempt was made to develop and optimize a solid dispersion system using different proportions of drug per carrier. Furthermore, the present study aims to clarify the potential for improving the solubility and dissolution rate of FB using hydrophilic polymers such as HPMC and HPMCAS by spray drying technology. MATERIALS AND METHODS HPMCAS-LF and HPMC (K100 Grade) were obtained from signet chemicals corporation, Mumbai. FB was procured from macleod’s pharmaceuticals, Mumbai. HPLC grade acetonitrile, hydrochloric acid (HCl), and dichloromethane were purchased from SD fine chemicals llimited, India. Methanol and potassium dihydrogen phosphate were purchased from rankem India. Phosphoric acid was purchased from fischer scientific limited, India. All chemicals and reagents utilized were of analytical grade. Triple distilled water (Rions, India) was used throughout the entire study. High-performance liquid chromatography (HPLC) analysis of FB Reversed-phase column based high-performance liquid chromatographic method (Nexera X2, Shimadzu, Japan) was used for quantification of FB in analytical media. The LC system consisted of a International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 11, Issue 4, 2019