Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate.

Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson-Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer-Peppas models.