A Oral Fast Dissolving Films Containing Lyophilized Labetalol HCL with Hydroxy Propyl β-Cyclodextrin/ Soluplus: Formulation Development, In Vitro Evaluation

Introduction: Labetalol HCL is an antihypertensive drug used to treat high blood pressure in the long term management of angina. Labetalol HCL is readily absorbed after oral administration. Labetalol HCl undergoes considerable hepatic first-pass metabolism due to its lipid-soluble nature.

Objective: The drug has an absolute bioavailability of approximately 25%. To overcome extensive hepatic first-pass metabolism the oral fast-dissolving film for labetalol HCL need to be developed. Lyophilized inclusion complexes of Labetalol HCL were developed with the hydrophilic carrier as Soluplus a Polyvinyl acetate polyethene glycol graft copolymer and Hydroxy Propyl β-cyclodextrin.

Experimental: Lyophilized inclusion complexes of labetalol: Soluplus and labetalol HCL: HP-β-CD were prepared with 1:0.5 weight ratios. The prepared lyophilized inclusion complexes were evaluated for solubility estimation, drug content, and In-vitro dissolution study.

Results: The prepared inclusion complexes were characterized by Fourier transforms infrared spectroscopy and differential scanning calorimetry. Characterization of the lyophilized complex showed changed crystallinity of labetalol HCL. The fast dissolving oral film of labetalol HCL was prepared by solvent casting method by adding film-forming polymer as HPMC K 4M/ PVA in different proportions and Propylene Glycol was used as a plasticizer. The prepared batches of films were evaluated for weight variation, tensile strength, folding, endurance, disintegration time, surface pH, and drug content uniformity. All formulations prepared among F5 and F 7 showed a better result as compared to other formulations.

Conclusion:  The study confirms the use of a lyophilized product containing Soluplus is best as that of HP-βCD for the preparation of fast dissolving film with HPMC/ PVA as film forming agent and propylene glycol as plasticizer respectively to improve dissolution rate and oral bioavailability of Labetalol HCl.