Promethazine Orally Disintegrating Tablet

Abstract

Orally Disintegrating Tablets (ODTs) which disintegrate rapidly (< one minute) in the mouth and do not require water for administration have become a very popular dosage form. Current methods of manufacturing ODTs are complex and require multiple processes. The specific aim of this study was to develop a simple, inexpensive method of manufacturing ODTs. Promethazine HCL, a highly soluble drug with an extremely bitter taste and an unpleasant anesthetic effect in the oral cavity, was chosen as a model drug. Simple low shear blending followed by direct compression was the preferred manufacturing method and was first examined. Taste-masking studies were conducted by directly mixing Promethazine with a number of substances. Taste-masking was assessed by dissolution studies and informal taste testing.

A 1:1 Magnesium Stearate: Promethazine mixture V-blended for one hour was effective in masking the bitter taste of this drug. The next step was to formulate an ODT which would rapidly disintegrate with this large amount of Magnesium Stearate. Magnesium Stearate is commonly known to increase both tablet friability and disintegration time, both of which are undesirable in an ODT dosage form. After initial failures with Mannitol, Dextrates, NF was the primary diluent utilized in this system. Tablets were produced with various combinations of disintegrants with various mechanisms of action. Tablets were also manufactured with a variety of materials with potential for producing a less friable tablet with a lower compression force. Flavor and sweetener trials were also conducted. A combination of Promethazine, Magnesium Stearate, Dextrates, and disintegrants was found to yield robust tablets (Friability < 1.0% with 0 broken at 25 rpm, for 4 minutes) with rapid disintegration (in vitro < 21 seconds, in vivo < one minute). Although the bitter taste was masked, the unpleasant anesthetic effect was not completely eliminated. The addition of 3.0% Menthol with sublimation post-tableting resulted in a visibly more porous tablet with shorter in vitro and in vivo disintegration times. These tablets yielded a pleasant taste without numbing. These tablets met compendial Dissolution and Content Uniformity requirements for conventional Promethazine tablets. These trials indicate an acceptable ODT can be produced using conventional excipients and simple blending followed by direct compression. In the case of Promethazine, the addition of Menthol followed by post-tableting sublimation was required to overcome the unpleasant numbing effect. While the sublimation of Menthol is an additional step, it only required a common laboratory oven and 48 hours.