International Journal of Biological Macromolecules 64 (2014) 347–352 Contents lists available at ScienceDirect International Journal of Biological Macromolecules jo ur nal homep age: www.elsevier.com/locate/ijbiomac Unfolding type gastroretentive film of Cinnarizine based on ethyl cellulose and hydroxypropylmethyl cellulose Shakuntla Verma a , Kalpana Nagpal b,∗ , S.K. Singh c , D.N. Mishra c a Jan Nayak Ch. Devilal Memorial College of Pharmacy, Sirsa 125055, Haryana, India b School of Pharmacy, Lovely Faculty of Applied Medical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India c Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India a r t i c l e i n f o Article history: Received 3 October 2013 Received in revised form 17 December 2013 Accepted 18 December 2013 Available online 24 December 2013 Keywords: Gastroretentive dosage form Hydroxypropyl cellulose, Ethyl cellulose a b s t r a c t The present work was based on the development and characterization of unfolding type gastro retentive dosage form appropriate for controlled release of Cinnarizine (CNZ), a drug with narrow therapeu- tic window. The drug loaded polymer film of biological macromolecules, i.e., ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC K15) was folded into hard gelatin capsules. The film was folded in different patterns for characterizing their unfolding behavior. The polymeric film revealed a fast release during the first hour followed by a more gradual drug release during a 12-h period following a non-Fickian diffusion process. Tensile strength of polymeric film was optimized using different amount (0.2–0.7 ml) of polyethylene glycol (PEG 400). Various physical parameters were studied for evaluating their perfor- mance as a gastroretentive dosage form. Drug and polymers were found to be compatible as revealed by differential scanning calorimetry (DSC) study and scanning electron micrograph (SEM) study revealed uniform dispersion of CNZ in polymeric matrices. The results indicate that unfolding type gastro retentive drug delivery system holds lots of potential for drug having stability problems in alkaline pH or are which mainly absorbed in acidic pH. © 2013 Elsevier B.V. All rights reserved. 1. Introduction The development of an oral controlled release formulation has an incredible impact on the drug delivery area especially for the drugs with a narrow absorption window but the limitation of this approach is insufficient retention of drug in the stomach [1–3]. In order to overcome this limitation, a number of strategies including, floating drug delivery system, mucoadhesives, co-administration of agents that alter the gastric motility have been developed [4,5]. Other approaches and drug carriers have been designed which unfold or expand in the stomach to form a complex geometric shape to obstruct its escape through the pyloric sphincter [6–8]. Com- bination of floating with the ability to expand by unfolding and swelling using blend of biodegradable polymers (hydrophilic and hydrophobic) is an alternative strategy to increase gastric residence time [9–11]. The present work is an effort to design a compressed device containing drug loaded polymeric film folded using differ- ent patterns into hard gelatin capsule. The capsule dissolves after ingestion and the compressed device release the film which then ∗ Corresponding author at: Pharmaceutics Domain, Lovely Professional Univer- sity, Phagwara, Punjab, India. Tel.: +91 9416729190. E-mail address: kalpana.18082@lpu.co.in (K. Nagpal). unfolds and the swelling usually results by osmotic absorption of gastric fluid [12]. Convenience of hard gelatin capsule is the major advantage of such type of dosage forms. In order to modify drug release through polymeric film design, there remain a number of issues includ- ing; selection of a polymer with the desired ability to unfold and expand in the stomach and complexity in formulating a drug loaded polymeric film [9]. CNZ, 1-(Diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine, is a Histamine H 1 receptor antagonist; antihistamines are widely used in treating nausea and vomiting associated with disorders of the inner ear such as Meniere’s disease and motion sickness. It works by blocking histamine receptors which are found in vari- ous sites in the body, including an area in the brain known as the vomiting center. CNZ is a Biopharmaceutical Classification System (BCS) Class II drug with poor aqueous solubility and permeability. It is mainly absorbed in the upper gastrointestinal tract and has a short half-life of 4 h [13,14]. The present work is an based on practical aspects of designing floating and unfolding type polymeric films which deliver imme- diate release (IR) to achieve the therapeutic drug concentration in a short period of time and controlled release to maintain the con- centration for the desired period of time and provide optimal drug release in upper gastrointestinal tract [15,16]. 0141-8130/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijbiomac.2013.12.030