FORMULATION AND EVALUATION OF RAMIPRIL MOUTH DISSOLVING FILMS Original Article JASVANTH E. 1 , TEJA D. 1 , MOUNIKA B. 1 , BUCHI N. NALLURI 1,2* 1 Department of Pharmaceutics and Biotechnology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, AP, India, 2 Received: 08 Jan 2019, Revised and Accepted: 18 Mar 2019 Siddhartha Pharma Innovation and Incubation Centre, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, AP, India Email: buchinalluri@yahoo.com ABSTRACT Objective: The present investigation was aimed at preparation and evaluation of mouth dissolving films (MDFs) of Ramipril to enhance patient convenience, compliance and to improve bioavailability. Methods: MDFs with 0.5% w/w Ramipril were prepared by a solvent casting method using a wet film applicator. The effects of film formers, wetting/solubilizing, saliva stimulating agents and film modifiers on the physicomechanical and in vitro Ramipril release from MDFs were evaluated. Results: The MDFs prepared were transparent, smooth and showed no re-crystallization upon storage. MDFs casted with hydroxypropyl methylcellulose (HPMC) E3 as film former and polyethylene glycol (PEG-400) as plasticizer showed superior Ramipril release rates and good physicomechanical properties when compared to MDFs with E5 and E15 as film formers. HPMC E3 MDFs with polyvinyl pyrrolidone K30 (PVP K30) and sodium lauryl sulphate (SLS) gave superior drug release properties than MDFs without PVP K30 and SLS. The HPMC E3 MDFs with citric acid (CA) as saliva stimulating and xylitol as soothing agent gave significantly superior in vitro drug release than the MDFs without CA and xylitol. Release kinetics data reveals diffusion as a drug release mechanism. Conclusion: From the obtained results, it can be concluded that the administration of Ramipril as MDF may provide a quick onset of action with enhanced oral bioavailability and therapeutic efficacy. Keywords: Hydroxy propyl methyl cellulose, Mouth dissolving films, Ramipril, Wet film applicator © 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.2019v11i3.32361 INTRODUCTION Hypertension is a chronic medical condition involving the elevated blood pressure levels. The delayed treatment of hypertension can lead to several other fatal disorders like congestive heart failure, kidney failure, stroke, etc. Moreover, the hypertension can occur in sudden, severe and acute attacks requiring immediate treatment [1]. Most of the anti-hypertensives are available in the oral or parenteral dosage forms, which have certain limitations such as swallowing and chocking difficulties, delayed onset of action, first pass metabolism, the requirement of skilled personnel and pain during delivery. These limitations and a need for the quicker onset of action with better patient acceptability has paved the way for the development of mouth dissolving films (MDFs) as an alternative to other dosage forms [2]. The MDFs are a very thin polymeric strip, which get hydrated instantly by saliva when placed on a patients tongue and then disintegrates and/or dissolves to release the medication within the pre-oral cavity [3]. The oral cavity composed of striated squamous epithelia with very thin membranes and fine capillary network provides 4-4000 times greater absorption than other parts of skin [4]. Ramipril is a new generation anti-hypertensive drug and is an angiotensin-converting enzyme (ACE) inhibitor. Ramipril is a prodrug/precursor which is converted into active metabolite ‘Ramiprilat’ in liver by carboxylesterase. Ramipril inhibits the actions of ACE lowering the production of angiotensin II [6]. This results in relaxation of arteriole smooth muscle leading to a decrease in total peripheral resistance, reducing blood pressure. Ramipril undergoes first-pass metabolism and has an oral bioavailability of about 28-30% [7]. Presently, Ramipril is marketed in the form of oral disintegrating tablets (ALTACE The drug is directly absorbed into the systemic circulation which by-passes the first pass metabolism, improving the bioavailability of the drug [5]. ® ) and immediate release tablets (CARDACE ® Few reports were published on formulation and evaluation of ramipril oral disintegrating, immediate release tablets, buccal patches and films. In most of the works reported so far, MDFs were prepared in petri plates, moulds etc. and the films were dried at 40- 45 °C overnight and this procedure may not result in uniformity of thickness and drug content and thereby, vary the drug release rates [7-12]. Moreover, no works on the influence of formulation variables like film thickness, polymer viscosities, surfactants and saliva stimulating agents were reported. Also, the reported works were not evaluated thoroughly for the drug loading effect on the re- crystallization and characterization using photographic, Fourier- transform infrared spectroscopy studies (FTIR), etc. By considering all the above facts, the present investigation was aimed to prepare MDFs using wet film applicator, an industrially scalable technique and evaluate them systematically. ). MATERIALS AND METHODS Materials Ramipril was obtained from Mylan Laboratories, Hyderabad. Hydroxypropyl methyl cellulose (HPMC E3, E5 and E15) samples were obtained from Colorcon Asia Ltd., India. Ethanol, polyvinyl pyrrolidone (PVP) K30, sodium lauryl sulphate (SLS) and citric acid (CA) were purchased from Loba Chemie, Mumbai. Pineapple flavour was obtained from Darwin laboratories, Vijayawada. Xylitol was obtained from Rouquette Laboratories, France. All the ingredients of analytical grade were used. Methods Preparation of artificial saliva Artificial saliva was prepared by dissolving 0.844 g of sodium chloride, 1.2 g of potassium chloride, 0.193 g of calcium chloride dehydrate, 0.111 g of magnesium chloride hexahydrate and 0.342 g of potassium phosphate dibasic one by one in 500 ml of distilled water and then the final volume was made up to 1000 ml using the distilled water. The pH was adjusted with 0.1N HCl to 5.7 [13]. Preparation of ramipril MDFs Ramipril MDFs were prepared as per the formula is given in table 1 by using the solvent casting method to a batch size of 5 g. Ramipril was dissolved in a mixture of solvents (water and ethanol) in a International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 11, Issue 3, 2019