Flexible New Dosage Forms Containing Carvedilol for the Treatment of Patients with Cardiovascular Disorders: Development, Stability, Palatability, and Microbiological Studies

Abstract

The development of formulations adapted to the patient’s age is a challenge in the pharmaceutical industry. Pediatric and geriatric patients may have difculties in swallowing oral medications when an adequate formulation is not available. Carvedilol is a poorly water-soluble drug used to treat cardiovascular problems; it is commercialized in several countries only as solid oral formulations, which are often manipulated at the point of administration to treat pediatric or geriatric patients. The purpose of this work was to obtain a new dosage form of Carvedilol using safe excipients, suitable for administration to pediatric and geriatric patients. To improve the solubility of Carvedilol, the efect of several factors was analyzed and optimized. Subsequently, to improve the physical stability of the formulations, two preparation methods were analyzed by adding HPMC. In “method 1,” HPMC was dissolved in bufer and incorporated into a mixture of Carvedilol-PEG 400, while in “method 2,” Carvedilol was solubilized in bufer containing PEG 400, and then, HPMC was added. Finally, microbiological tests were performed to the stable formulations. The factors “pH value” and “concentration of PEG” afected the solubility of Carvedilol. A formulation containing Carvedilol (3 mg/mL), pH=3, PEG 400 (15% v/v), and HPMC (0.25% w/v) prepared by method 2 was stable for 180 days at 4 °C while those containing Carvedilol (5 mg/mL), pH=3, PEG 400 (27% v/v), and HPMC (0.5% w/v), prepared by method 2, were stable for 180 days at 4 and 25°C. These oral liquid formulations were physicochemical and microbiologically stable for 6 months.