Evaluation of Hydroxypropyl Cellulose for Orally Disintegrating Film Drug Application

SUMMARY Hydroxypropyl cellulose (HPC) is a watersoluble polymer which is solublized by introducing hydroxypropyl group and thus hindering the hydrogen bonds of hydroxyl groups of cellulose. Also, it is known HPC has film formation properties with excellent plasticity. In this study, we evaluated effects of drugs, excipients and molecular weight of HPC on Orally Disintegrating Film (ODF) prepared by using HPC as base material. As a result of evaluation, HPC was found to be usable material for ODF applications. INTRODUCTION Oral dosage is thought as the most desirable medication method since it is easy and non-invasive. Tablet, powder, capsule etc. are mainly used for oral dosage forms. However, pediatric and geriatric patients experience difficulties in swallowing oral dosage forms, due to lower swallowing abilities or illness. Orally disintegrating tablets (ODTs) disintegrate quickly in the oral cavity without water and can be taken easily even by people with difficulties in swallowing. However, preparation of ODTs achieving both enough tablet hardness and quick disintegration is challenging and special tablet machine or technology may be required. Orally disintegrating films (ODFs) offer an alternative medication route. Used in the oral care markets as mouth freshener, they have been evolved for the pharmaceutical market. ODFs contain water soluble polymers, allowing quick hydration and disintegration. These films are flexible and less fragile compared to ODTs and possess advantages of durability and portability. Hydroxypropyl cellulose (HPC) is widely used as binder and film coating agent for various pharmaceutical processing techniques owing to its chemically inert nature. HPC is water and organic solvent soluble polymer, exhibits film-forming properties with excellent plasticity for easy handling. In this study, ODFs using HPC as a base material have been prepared and their effect on film properties by formulating drugs and other excipients has been evaluated. EXPERIMENTAL METHODS Materials HPC-SL was used as a base material of ODF. Erythritol, glucose, trehalose, calcium carbonate (CaCO3), microcrystalline cellulose (MCC), crospovidone (cl-PVP), croscarmellose sodium and low-substituted hydroxypropyl cellulose (L-HPC) were evaluated as excipients. Ascorbic acid (VC), acetaminophen (AAP) and ibuprofen (IBU), which have different level of solubility, were used as model drugs. Their solubility is 40, 14 and 0.049mg/mL respectively. Preparation Method of HPC Film Evaluation of Disintegratability Evaluation of Film Strength Film strength was calculated based on tensile strength measured by creep meter. RESULTS AND DISCUSSION 1. Effect of HPC-SL Concentration Increasing HPC-SL concentration led to increased disintegration time while tensile strength was not affected. It was observed that film thickness increased in proportion to HPC concentration. 2. Effect of Drug Loaded Fig. 1: Effect of Drug Loaded on HPC Film The results showed tensile strength was reduced by addition of drug. It is because binding strength between HPC molecules was hindered by drugs molecule. On the other hand, disintegration time was increased by addition of drugs especially in the case of AAP or IBU which are lower soluble drugs (Fig.1) 3. Effect of Excipients formulated Fig. 2: Effect of selected excipients on HPC Film The results showed disintegration time and tensile strength were not affected or reduced by addition of excipients. Also, formulated excipients did not show remarkable improvement in disintegration time. (Fig.2) 4. Effect of Excipients on Disintegration Time in the presence of Ibuprofen Fig. 3: Effect of Excipients on Disintegration Time The results showed when CaCO3 was added, disintegration time was reduced by 1/3 while tensile strength was slightly improved. Not much difference was seen for both disintegration time and tensile strength when trehalose and MCC were added (Fig. 3). CONCLUSION The results showed that disintegration time of HPC film tended to increase in proportion to increasing film thickness depending on HPC contents, while tensile strength was independent. By formulating IBU, the most hydrophobic drug tested, much increased disintegration time of film was observed. The disintegration time was reduced by addition of CaCO3. Based on these results it was suggested that ODF could be designed and prepared by using HPC as basic material. REFERENCES 1. Umemura, K., Yamakawa, R., Takeuchi, Y., Takeuchi, H. Usability of PVA Co-polymer as a New Type of Film Former for Orally Disintegrating Film Dosage Form. The 25th Annual Meeting of the Academy of Pharmaceutical Science and Technology, Japan (2010) 2. Takeuchi, H., Yamakawa, R., Nishimatsu, T., Takeuchi, Y., Hayakawa, K., Maruyama, N. Design of rapidly disintegrating drug delivery films for oral doses with hydoxypropyl methylcellulose. J. DRUG DEL. SCI. TECH., 23 (5) 471-475 2013