Development of a melting tablet containing promethazine HCl against motion sickness

Abstract

The purpose of this study was to design a 'Traveller Friendly Drug Delivery System' for PM-HCl. Conventional promethazine (PM-HCl) tablets are bitter, need to be taken 1 h before symptoms and water is also needed. Taste-masked granules were produced with Eudragit E100 by extrusion, and analyzed with FTIR, DSC, and XRD. Tablets formulated from granules by direct compression using Ac-Di-Sol, Polyplasdone-XL, Primojel and ion-exchanger Tulsion339 and evaluated for mass uniformity, friability, tensile strength, drug content uniformity, water absorption ratio, in-vitro and in-vivo disintegration time and in-vitro dissolution studies. The observed drug-polymer interactions and reduced crystallinity may be reasons for increased dissolution rates. The formulated tablets were disintegrated within 15 s. Tablets (25 mg PM-HCl) with Ac-Di-Sol (4%) showed complete release within 1 min, while marketed conventional tablets (Phenergan; Rhone-Poulec) release 25% during the same period. A preliminary stability studies for the prepared tablets carried at 30 +/- 2 degrees C/60 +/- 5% RH, and 40 +/- 2 degrees C/75 +/- 5%RH for 3 months showed no significant changes in the tablets quality at 30 +/- 2 degrees C/60 +/- 5% RH. However, at 40 +/- 2 degrees C/75 +/- 5%RH marked increase in in-vitro disintegration time, tensile strength and decrease in friability and water absorption ratio was found. The present studies indicate the abilities of Eudragit E 100 for taste masking and improving the dissolution profile of PM-HCl after complexation. In addition, by employing cost effective direct compression method, fast-dissolving tablets of 400 mg total weight with an acceptable quality could be prepared.

Fig. 1

Scheme of preparation of taste masked granules and melting tablets

Fig. 2

Comparison of D _30s values of Promethazine HCl from Eudragit^®E 100 and Eudragit ^®RD 100 (±S.D. n = 3)

Fig. 3

DSC thermogram of PM-HCl, Eudragit^® E100 and PM-HCl: Eudragit^® E 100 complex

Fig. 4

FTIR spectra of PM-HCl, Eudragit^® E 100 and PM-HCl: Eudragit^® E 100 complex

Fig. 5

X-Ray diffraction pattern of PM-HCl, Eudragit^® E 100 and PM-HCl: Eudragit^® E 100 complex

Fig. 6

Comparison of dissolution profile of Pure PM-HCl, control tablet and conventional tablet of PM-HCl (Phenergan^®) (±S.D. n = 3)

Fig. 7

Dissolution profiles for tablet prepared by direct compression technology using Polyplasdone^®-XL, Ac-Di-Sol, Primojel^® and Tulsion^® 339 as superdisintegrant