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In this study we aimed to develop a semi-solid formulation of polymeric nanoparticles loaded with adapalene to enhance the efficacy and improve the skin tolerability in acne therapy. An amphiphilic and biocompatible copolymer that self-assembles to nanospheres (known as TyroSpheres) was used to encapsulate adapalene and increase its solubility. A water-soluble viscous agent was applied to prepare a gel formulation of adapalene-loaded TyroSpheres (aapalene-TyroSphere). Particle size, morphology, homogeneity, and rheological characteristics of the adapalene-TyroSphere gel formulations were studied. The formulation with the preferred physical and structural properties was further investigated for in vitro skin irritation and in vivo comedolytic activity in a rhino mouse model. Based on the in vitro skin irritation study encapsulation of adapalene in TyroSphere significantly decreased secretion of pro-inflammatory cytokines (IL-1α and IL-8), confirming that the TyroSphere formulation of adapalene is less irritant than the commercial gel (Differin). TyroSphere gel formulation of adapalene improved the comedolytic properties of the formulation by significantly reducing the size of open utricles in rhino mice compared to Differin treatment. Using TyroSpheres, we were able to develop an alternative topical formulation of adapalene, which is potentially less irritant and more potent than the commercial product.

To date, effective treatment, prophylaxis, and control of tuberculosis (TB) infection is mainly dependent on the use of drugs. However, patient noncompliance with prescribed anti-TB treatment schemes remains a major problem confronting successful pharmacotherapeutic outcomes. Thus, the development of alternative delivery systems that can improve adherence for the existing anti-TB bioactives has been intensified in recent times. The aim of this investigation was to engineer an optimal, thermodynamically stable oral film (OF) formulation containing a key anti-TB agent, pyrazinamide (PYZ), employing molecular modeling and experimental tools. Four PYZ-loaded film variants (OF 1, OF 2, OF 3, OF 4) were constructed in silico and then prepared in vitro using the Accelrys Materials Studio software and solvent casting method, respectively. Screening and selection of the optimal OF was based on the computation of the total interaction energy (ET), kinetic energy (EK), solubility parameter (S), and cohesive energy density (CED) as well as determining mass, thickness, dissolution and disintegration times, dissolution pH, drug loading capacity, and surface morphology in vitro. OF 2 was selected as the optimal formulation as it displayed the lowest ET (-8006.28 kcal/mol), dissolution time (9.96 min), disintegration time (56.49 s), and weight (39.33 mg); moderate EK (1052.98 kcal/mol); highest S (44.55 (J/cm(3))(0.5)) and CED (1.99 × 10(9) J/m(3)), slim dimension (166 μm), good and unvarying drug loading capacity (98.04%), acceptable dissolution pH (6.70), and well-layered surface topography. The drug release behavior of the optimal OF 2 was best elucidated with the zero order (R(2) = 0.97) and Korsmeyer-Peppas (R(2) = 0.99) models. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) analyses showed that OF 2 was made of physically mixed multiple component polymeric and nonpolymeric compounds. OF 2 was semicrystalline in nature and displayed a dual phased ex vivo mucosal permeation pattern. In silico and in vitro physicomechanical quantities revealed OF 2's flexibility, robustness, and compressibility. OF 2 was most stable under controlled environmental humidity, pressure, and temperature conditions in silico and in vitro. OF 2 was potentially non-cytotoxic and biocompatible. Succinctly, this work demonstrated the applicability of a combination of atomistic molecular mechanics and dynamics calculations as well as experimental analyses to the fabrication, screening, optimization, and characterization of drug formulations. Lastly, the fabricated OF 2 formulation can function as a potential alternative for the effective loading and delivery of PYZ.