Evaluation and optimization of preparative variables for controlled-release floating microspheres of...

Levodopa, a prodrug of dopamine, is the first line drug in the treatment of Parkinson's disease. All current levodopa products are formulated in combination with aromatic amino acid decarboxylase inhibitors such as carbidopa or benserazide to prevent the peripheral metabolism of levodopa. The objective of the present investigation was to produce floating microspheres of carbidopa (CD)/levodopa (LD) to enhance their efficacy by increasing their gastric residence time, which is major technique to improve efficacy of narrow absorption window drugs. The microspheres were prepared by the o/w emulsion-solvent diffusion method using polymers hydroxypropylmethyl cellulose K15 M (HPMC K15 M) and ethyl cellulose (EC). The effects of various formulation and process variables on the particle size, in vitro floating behavior, percent drug entrapment, and in vitro drug release were studied. The size and surface morphology of prepared microspheres were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression analysis. The prepared microspheres exhibited prolonged drug release (approximately 10h) and remained buoyant for >12 h. Spherical and smooth-surfaced microspheres with encapsulation efficiency ranging from 43% to 80% were obtained. In vitro studies demonstrated diffusion-controlled drug release from the microspheres.