Review Article HPMC AS CAPSULE SHELL MATERIAL: PHYSICOCHEMICAL, PHARMACEUTICAL AND BIOPHARMACEUTICAL PROPERTIES SUTAPA BISWAS MAJEE * , DHRUTI AVLANI, GOPA ROY BISWAS Division of Pharmaceutics, NSHM Knowledge Campus, Kolkata-Group of Institutions 124 B L Saha Road, Kolkata 700053 West Bengal, India Email: sutapabiswas2001@yahoo.co.in Received: 14 Jun 2017 Revised and Accepted: 31 Aug 2017 ABSTRACT The most common instability problem of gelatin capsules arises from negative impact of extremes of temperature and especially atmospheric relative humidity on the mechanical integrity of the capsule shells with adverse effect extended even to the fill material. Moreover, choice of fill materials is highly restricted either due to their specific chemical structure, physical state or hygroscopicity. Additional reports of unpredictable disintegration and dissolution of filled hard gelatin capsules in experimental studies have prompted the search for a better alternative capsule shell material. The present review aims to provide an overview on the physicochemical, pharmaceutical and biopharmaceutical properties of hydroxypropyl methylcellulose (HPMC) as capsule shell material and perform comparative evaluation of HPMC and gelatin in terms of in vitro/in vivo performance and storage stability. HPMC capsule provides a highly flexible and widely acceptable platform capable of solving numerous challenges currently facing the pharmaceutical and nutraceutical industries and expands the possibilities for selection of different types of fill materials. The current topic introduces a new section on influence of various factors on in vitro dissolution of HPMC capsules. Delayed in vitro disintegration/dissolution of HPMC capsules in aqueous medium does not produce any negative effect in vivo. However, advancements in the processes of production and filling of HPMC capsule shells and detailed studies on effects of various parameters on their in vitro/in vivo dissolution would establish their supremacy over hard gelatin capsules in future. Keywords: Gelatin, HPMC, Formaldehyde challenge test, In vitro dissolution, Stability study © 2017 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/ijpps.2017v9i10.20707 INTRODUCTION Capsule, a versatile unit solid dosage form for oral administration is designed to enclose solid, liquid or semi-solid mixture of active pharmaceutical ingredient (API) and suitable excipients in hard gelatin shells or in soft shells of gelatin [1]. Capsule-based time controlled pulsatile drug delivery system has been designed and has ushered a new era in chronotherapeutics for synchronisation of drug delivery in management of diseases with circadian rhythm [2]. Capsules are capable of providing protection to encapsulated drug from deterioration induced by atmospheric oxygen, light, moisture etc. owing to the barrier effects of shell [3]. Gelatin is the most widely used capsule shell material because of its non-toxicity, solubility in biological fluids at body temperature, ability to undergo thermal gelation and form a strong, flexible and homogeneous film [4]. Gelatin is widely used for stabilisation of pharmaceutical suspensions and also in design of novel drug delivery systems such as wafers [5, 6]. However, few inherent characteristics of gelatin responsible for compromised in vitro stability of capsule and somewhat unpredictable disintegration and dissolution in experimental studies have given rise to the need for a better alternative for capsule shell material. Problems associated with selection and performance of gelatin are mentioned below. Cross linking Since, gelatin is a naturally occurring protein, it is susceptible to hydrolysis producing amino acids. Therefore, it can be reactive towards molecules of varying chemical structures mainly aldehydes or any formulation component possessing aldehydic functional group, reducing sugars, metal ions, plasticizers and preservatives. The amphoteric nature of gelatin may lead to incompatibility with anionic and cationic polymeric excipients as well as surfactants [7, 8]. Some of the commonly used excipients in preparation of various dosage forms such as fats, polyethylene glycol and its ethers, aliphatic alcohols or phenols, polysorbates and esters of unsaturated fatty acids can undergo auto-oxidation to form aldehydes. The aldehydic end– products of degradation can cross-link with gelatin resulting in excipient-excipient interaction, formation of insoluble skin or pellicle on the gelatin shell and ultimately retarded dissolution [9]. A well known example of excipient-induced cross-linking of gelatin is that due to formaldehyde produced as a result of the decomposition of lactose. Environmental factors such as high humidity, high temperature and UV light can also induce cross-linking reactions [8]. Moisture content and stability problem Water (13%w/w to 16%w/w) in the gelatin film acts as a plasticiser and enables the formation of a tough but flexible film. Change in relative humidity of the environment may either lead to brittle or soggy shells with sometimes a negative impact on the fill material [3, 4, 9, 10]. Sensitivity of gelatin to extremes of humidity is the major area of concern for use of capsules in too humid/dry climates. Temperature-dependent disintegration/dissolution Temperature is a key parameter that should be strictly controlled during disintegration and dissolution testing of capsules. Problem arises when temperature falls below 37 °C, since gelatin solubility decreases. At temperature below 30 °C, the capsule shells are insoluble and simply absorb water, swell and distort. Because of this, compendia and Pharmacopoeia of different countries have set a limit of 37 °C±1 °C for carrying out these tests on capsules [3, 11]. Religious perspective The animal source of gelatin is an area of concern for some sections of population such as vegetarians or vegans and people belonging to certain religious or ethnic groups who practice diets that forbid the use of animal products [12]. Special manufacturing conditions Liquid and semi solid filling cannot be done in hard gelatin capsules. Although, soft gelatin capsules provide a better alternative for such fill materials, special manufacturing conditions and stringent environmental control of temperature and humidity are required for their production. During the process of capsulation, the temperature and humidity of the air are maintained at 57-59 °F and 20% RH. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 9, Issue 10, 2017