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

The development of formulations adapted to the patient's age is a challenge in the pharmaceutical industry. Pediatric and geriatric patients may have difficulties 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 effect 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 buffer and incorporated into a mixture of Carvedilol-PEG 400, while in method 2, Carvedilol was solubilized in buffer 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 affected 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 degrees 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 degrees C. These oral liquid formulations were physicochemical and microbiologically stable for 6 months.

Automated summary

The development of age-appropriate formulations in the pharmaceutical industry is challenging, especially for pediatric and geriatric patients who may have difficulty swallowing oral medications. This study aimed to obtain a new dosage form of Carvedilol suitable for pediatric and geriatric patients. The solubility of Carvedilol was improved by analyzing and optimizing various factors, and the physical stability of the formulations was enhanced by adding HPMC. Microbiological tests were conducted to assess the stability of the formulations.