Purpose: There has been an increase in infants and children infected with human immunodeﬁciency virus (HIV) over the past decades. The high mortality rate associated with pediatric HIV in this vulnerable and neglected population is partially due to the lack of age-appropriate oral drug products for pediatric patients. To address this highly unmet medical need, the present research developed a child-friendly and palatable oral fast-dissolving film for pediatric AIDS patients.
Methods: Lopinavir (LPV) and ritonavir (RTV), HIV protease inhibitor antiretroviral drugs, were used as the model compounds. Cyclodextrin was incorporated into film casting materials to improve dissolution and palatability of the drugs. LPV/RTV (4/1, w/w) loaded fast-dissolving films were prepared via a solvent casting method, and a partial factorial design was utilized to study the critical formulation and process parameters of the fast-dissolving films. The appearance, thickness, drug loading, dissolution rate were investigated. Solid state of the drugs in the fabricated films was characterized via X-ray powder diffraction (XRD) and polarized microscope. Furthermore, taste assessment of LPV/RTV loaded films was performed.
Results: An analytical method that is capable of simultaneously detecting antiretroviral drugs (i.e. LPV and RTV) was developed and validated. Following the formulation optimization, HPMC E5, glycerin, and β-cyclodextrin were selected as the film-forming polymer, the plasticizer, and the inclusion polymer, respectively. The prepared films had a smooth physical appearance with an average thickness of 80 μm (Figure 1), and satisfactory mechanical properties. The content uniformity (percentage of label claim) of the prepared films was within 98-102%. Solid state characterization results indicated that amorphous drugs existed in the films (Figure 2). It was observed that the average disintegrated time of the prepared films was about 50 s, and nearly 100% of in vitro drug release was obtained within 10 minutes. Compared to pure drugs, the in vitro dissolution profiles of both LPV and RTV were drastically improved. Moreover, the bitterness of the drugs was successfully masked.
Conclusion: A novel LPV/RTV oral fast-dissolving film with smooth surface, high drug loading, as well as improved dissolution and palatability was successfully developed in the present study. This oral fast-dissolving film is a promising child-friendly and palatable oral dosage form for pediatric AIDS patients.
Acknowledgement: Support was provided by the IPEC-Americas Foundation Emerging Researcher Award.