Compression Coated Diphenhydramine tablets: Tablets with at least 8 hour zero-order drug release

Abstract

Diphenhydramine is a first-generation antihistamine medication introduced in the mid 1940s used for allergic rhinitis. The main goal of this project was to develop and manufacture tablets with zero-order release for at least 8 hours containing 50 mg of diphenhydramine. In short, zero-order release means that equal amounts of active ingredient is released per time unit until the dosage is fully released. This can be useful for drugs that have a narrow therapeutic index and a short half-life. The benefit of extended-release formulations is to achieve consistent plasma concentration throughout the dose which reduces side effects and improves patient adherence among other benefits.To obtain this extended-release, a method known as compression coated tablets or tablet-in-tablet was used which consists of an inner layer and an outer layer. The outer layer is meant to have prolonged-release properties and a near zero-order curve and the inner layer having fast-release properties acting as a booster, maintaining the zero-order release.Eight different double layered formulations were prepared and tested for the desired release profile using a mix of excipients in different proportions. Formulation F7 was chosen as the final formulation having an inner layer consisting of DPH-HCl (50%), HPMC K100M (5%), lactose (44%) and MgSt (1%) and an outer layer consisting of DPH (8.33%), HPMC K100M (30%), lactose (50.67%), PVP K30 (10%) and MgSt (1%). This formulation was chosen as it had a dissolution profile most fitting the objective of the project and was subsequently tested according to the European Pharmacopeia with all tablets passing.