Cross linked plantain starch-urea as a polymer in matrix tablets of ambroxol hydrochloride

Adenike Okunlola,Adenike Temidayo Adedeji

doi:10.5920/bjpharm.774

Abstract

Plantain (Musa paradisiaca) starch, prepared as crosslinked starch-urea (CSU), was utilized in the formulation of matrix tablets of ambroxol hydrochloride. CSU was synthesized by gelatinization of plantain starch in urea, crosslinked with calcium chloride. Native starch and CSU were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), chemical and material properties. Ambroxol hydrochloride tablets were prepared with CSU, 1:1 blend of CSU and Hydroxyl propyl methylcellulose (HPMC K15M) and HPMC K15M alone at 20, 30 and 40%w/w. The 32 factorial design was used to optimize tablets using polymer type (X1) and polymer concentration (X2) as independent variables, crushing strength-friability ratio (CSFR) and time for 80% drug release (t80) as responses. The SEM revealed changes in the ovoid granules of native starch to larger, irregular granules of CSU. The XRD spectra revealed a more crystalline CSU with higher swelling and better flow. Polymer type had more influence on CSFR and t80. The optimized batch containing CSU at 40 %w/w exhibited the highest values of CSFR and drug release. Experimental responses of the optimised batch had close proximity with the predicted value. Cross-linked plantain starch-urea polymer was found suitable as a polymer in matrix tablets of ambroxol hydrochloride.

Highlights

A matrix drug delivery system is composed of a drug that is either dissolved or dispersed within a polymeric matrix (Jones, 2004; Nokhodchi et al, 2012)
Matrix tablets offer a wide range of advantages over the conventional dosage form; they are easy to manufacture while frequency of dosing is reduced, since the drug is released over a longer period of time
Even though synthetic polymers or semisynthetic polymers such as Hydroxypropyl methylcellulose (HPMC) appear to be popular choices for formulation of hydrophilic matrix system, starch is another widely used excipient in the pharmaceutical industry owing to its availability, versatility, inert nature, cost effectiveness, biodegradability and adaptability to various modifications

Summary

INTRODUCTION

A matrix drug delivery system is composed of a drug that is either dissolved or dispersed within a polymeric matrix (Jones, 2004; Nokhodchi et al, 2012). Matrix tablets offer a wide range of advantages over the conventional dosage form; they are easy to manufacture while frequency of dosing is reduced, since the drug is released over a longer period of time This is of importance to patients with chronic illnesses who require the plasma drug concentrations to be within therapeutic range. Matrix tablets of ambroxol hydrochloride were formulated using cross-linked plantain starch-urea polymer (CSU), combination blend of CSU with Hydroxyl propyl methyl cellulose, HPMC K15M (1:1) and HPMC alone. Sustained release formulations of ambroxol hydrochloride have been developed in order to reduce the frequency of administration to once daily This will offer the advantages of sustained blood levels, attenuation of adverse effects and improved patient compliance. A simple and cost effective approach to control the release of the drug is to disperse it within an inert polymeric matrix and the use of plantain starch-urea as hydrophilic matrices offer an appealing option. Optimized tablets were prepared using a 32 full factorial design to determine the effects of selected independent variables, type of polymer (X1) and polymer concentration (X2), on dependent variables crushing strength-friability ratio (CSFR) and t80

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSIONS