Optimization and Characterization of Hot-Melt Extruded Anti-Inflammatory and Local Anesthetic Bio-Adhesive Semisolid Formulation Using Design of Experiments (DoE)

Hot melt extrusion is a versatile continuous manufacturing process extensively investigated for its applications with production of oral solid dosage forms, the aim of this study was to venture the applicability of HME in continuous manufacturing of topical semi-solid ointment formulations. Novel combination of a topical corticosteroid (Triamcinolone Acetonide) and local anesthetic (Lidocaine hydrochloride) were selected to be formulated with a water-soluble ointment base consisting of PEG 4000, PEG 1500 and Propylene glycol after performing appropriate drug-excipient compatibility studies. To determine the ratios of the solid to liquid components of the macrogol base, ‘quality by design’ approach was employed by using design of experiments for formulation selection. Three formulations were selected using texture (work of adhesion and stiffness), pH and drug content uniformity as critical quality attributes from the design space of the formulation. These three selected formulations were then produced by conventional fusion method and simultaneously by HME using a modified screw configuration. Produced ointments were subjected to further characterizations including texture analysis (work of adhesion and stiffness), pH, drug content uniformity of the formulations, differential scanning calorimetry and finally to exhibit the release profile of the formulation in vitro drug release testing was conducted. All the final formulations depicted characteristics parallel to the set Quality Target Product Profile. Moreover, Formulations prepared by HME displayed better texture, uniformity and drug release characteristics in contrast with conventionally prepared ointments and hence HME can be considered as a useful continuous manufacturing technique for semi-solid manufacturing