RESEARCH ARTICLE Formulation development, optimization, and evaluation of sustained release tablet of valacyclovir hydrochloride by combined approach of floating and swelling for better gastric retention Pratik Upadhyay & Kunal Nayak & Kaushika Patel & Jaymin Patel & Shreeraj Shah & Jayant Deshpande Published online: 25 October 2014 # Controlled Release Society 2014 Abstract The present study is intended to enhance gastric retention of sustained release tablet of valacyclovir hydrochlo- ride by combined approach of floating and swelling. The tablets are prepared by direct compression method. Polyeth- ylene oxide (Polyox WSR 303) is selected as the swelling matrix agent. Sodium starch glycolate (SSG) is used as swell- ing enhancer, and sodium bicarbonate is used as an efferves- cent agent for floating. A 3 2 full factorial design is applied to systematically optimize the formulation. The concentration of Polyox WSR 303 (X 1 ) and concentration of SSG (X 2 ) are selected as independent variables. The percentage drug release at 12 h, floating lag time, and maximum percentage swelling are selected as dependent variables. Formulations are evalu- ated for hardness, friability, floating lag time, total floating time, percentage swelling, in vitro drug release, and in vivo floating study. The results indicated that X 1 and X 2 signifi- cantly affected the drug release properties, floating lag times, and maximum percentage swelling. Release rate decreases as the concentration of Polyox increased. Regression analysis and numerical optimization are performed to identify the best formulation. Formulation F5 prepared with Polyox WSR 303 (15 %) and SSG (10 %) is found to be the best formulation. F5 followed zero-order release mechanism. Swelling and floating gastroretentive tablets of valacyclovir HCl are successfully formulated with controlled delivery to stomach with an aim of increasing the mean residence time in the upper part of GIT where the drug has its absorption window. Keywords Floating . Gastroretentive . Swelling . Polyox WSR 303 . Sustained release . Valacyclovir HCl Introduction An appropriately deliberated controlled release dosage form is advantageous than conventional release dosage form by pro- viding therapeutic amount of the drug in a desirable manner for a longer period of time that elicits pharmacological action at a reduced dosage and consequently minimized unwanted adverse effects [1]. Oral route is by far the most preferable for drug delivery due to its ease of administration, better patient compliance, and flexibility in formulation [1, 2]. Development of oral controlled release tablet is an intricate task for the formulation scientists because of its malfunction to restrain and localize in the gastrointestinal tract [3]. Considerable efforts have been made to design oral controlled drug delivery systems that produce more predictable and increased bioavail- ability of drugs [4]. Under certain circumstances, prolonging the gastric resi- dence of the drug is favorable for achieving greater therapeutic consequences [5], e.g., for those drugs which are absorbed in the proximal part of the GI tract, locally acting in the stomach, and are less soluble or are degraded by alkaline pH [6]. Recent approaches executed to increase the gastric residence time of the drug include bioadhesive system, swelling system, low or high density system, magnetic system, unfoldable system, and super porous biodegradable hydrogel system [7]. Insight from the formulation technology, the low-density floating drug delivery system is considerably a logical ap- proach [8] but is effective only when the fluid level in the stomach is adequately high [9], and as the stomach drains, the P. Upadhyay (*) : K. Nayak : K. Patel : J. Patel : S. Shah : J. Deshpande Department of Pharmaceutical Technology, L. J. Institute of Pharmacy, Ahmedabad, Gujarat 382210, India e-mail: pratik_pharmacist@yahoo.com Drug Deliv. and Transl. Res. (2014) 4:452–464 DOI 10.1007/s13346-014-0207-x