Performance testing of medicated chewing gums with the goal of establishing in vitro in vivo correlation
Date issued
Authors
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
License
Abstract
Evaluation of the performance of medicated chewing gum requires suitable chewing apparatus to simulate the masticatory action. In an in vitro environment, the release of any active pharmaceutical ingredient (API) present in chewing gum formulation is controlled by various apparatus parameters that include the distance between chewing jaws, rate of chewing (chewing frequency) and the twisting angle of chewing jaws. In this study, influence of all these factors in various combinations was evaluated using Apparatus A and B described in the chapter 2.9.25 of the European Pharmacopeia (Ph. Eur.) for commercially available nicotine based chewing gum products.
Nicotine containing chewing gums were chosen as a model drug product to develop the in vitro drug release methodology and to assess the suitability of the apparatus. The in vitro release testing methodology was further extended to Dimenhydrinate and Caffeine containing chewing gum products using Apparatus B due to its commercial availability. The in vitro release pattern from various chewing gum products indicated that the release of API(s) vary with respect to the product, apparatus type and setup parameter. Interchangeability of the apparatus for nicotine gum product was found only for a few apparatus parameters verified using the similarity test (f2) statistical approach. For most of the investigated gum products, highest release of the active was observed for the apparatus parameters with smallest chewing distance (apparatus A: 0.3 mm/3 mm, apparatus B: 1.4 mm), highest twisting angle 40° (apparatus B) and chewing frequency of 60 strokes/min (apparatus A and B). Verification of in vitro release methodology was performed using in vivo chew out approach and also from the in vivo clinical data. Correlation between the in vitro data and in vivo chew out data was observed. No in vitro in vivo correlation (IVIVC) could be established using the in vitro and in vivo clinical data.
Further experiments were performed with a goal of manufacturing nicotine containing chewing gums using a tableting technique. As a first step, a batch process to load nicotine onto a strong cation exchange resin was optimized. Nicotine to resin ratio was maintained 1:4. The nicotine loaded resins were coated using pH neutral polymer Eudragit RS 100. In vitro drug release experiment was used to assess the performance. The uncoated and Eudragit RS 100 coated resin complex were used as an API for manufacturing nicotine chewing gums. Various combinations of formulations containing different gumbases and excipients were used to formulate nicotine gum formulations. It was shown from the experiments that the release of nicotine salt > uncoated nicotine resinate > coated nicotine resinate present in gum formulations. Using this approach, possibilities to manufacture chewing gums by conventional tableting technique and to tailor the release of nicotine was explored. This work may provide a basis for further research to incorporate many more APIs of different physicochemical properties in chewing gum formulations.