title: Design and Evaluation of Topical Diclofenac Sodium Gel Using Hot Melt Extrusion Technology as a Continuous Manufacturing Process with Kolliphor® P407.
abstract: The aim of the present context was to develop and evaluate a Kolliphor® P407-based transdermal gel formulation of diclofenac sodium by hot melt extrusion (HME) technology; central composite design was used to optimize the formulation process. In this study, we have explored first time ever HME as an industrially feasible and continuous manufacturing technology for the manufacturing of gel formulation using Kolliphor® P407 and Kollisolv® PEG400 as a gel base. Diclofenac sodium was used as a model drug. The HME parameters such as feeding rate, screw speed, and barrel temperature were crucial for the semisolid product development, and were optimized after preliminary trials. For the processing of the gel formulation by HME, a modified screw design was used to obtain a uniform product. The obtained product was evaluated for physicochemical characterization such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), pH measurement, rheology, surface tension, and texture profile analysis. Moreover, it was analyzed for general appearance, spreadibility, surface morphology, and drug content. The optimized gel formulation showed homogeneity and transparent film when applied on a glass slide under microscope, pH was 7.02 and uniform drug content of 100.04 ± 2.74 (SD = 3). The DSC and XRD analysis of the HME gel formulation showed complete melting of crystalline API into an amorphous form. The Kolliphor® P407 and Kollisolv® PEG400 formed excellent gel formulation using HME with consistent viscoelastic properties of the product. An improved drug release was found for the HME gel, which showed a 100% drug release than that of a marketed product which showed only 88% of drug release at the end of 12 h. The Flux value of the HME gel was 106 than that of a marketed formulation, which showed only about 60 value, inferring a significant difference (P < 0.05) at the end of 1 h. This study demonstrates a novel application of the hot melt extrusion process for manufacturing of topical semisolid products.
authors.affiliation: BASF India Ltd, Pharma Solutions, Plot No. 12, TTC Area, Thane Belapur Road, Turbhe, Navi Mumbai, 400705, India. jaywantpawar.ict@gmail.com.|Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai, 400019, India. jaywantpawar.ict@gmail.com.
authors.forename: Jaywant
authors.identifier: http://orcid.org/0000-0002-7416-2446
authors.initials: J
authors.lastname: Pawar
authors.affiliation: BASF India Ltd, Pharma Solutions, Plot No. 12, TTC Area, Thane Belapur Road, Turbhe, Navi Mumbai, 400705, India.
authors.forename: Rajkiran
authors.initials: R
authors.lastname: Narkhede
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, University under Section-3 of UGC Act-1956, Elite Status & Centre of Excellence - Govt. of Maharashtra, N. P. Marg, Matunga, Mumbai, 400019, India.
authors.forename: Purnima
authors.initials: P
authors.lastname: Amin
authors.affiliation: BASF India Ltd, Pharma Solutions, Plot No. 12, TTC Area, Thane Belapur Road, Turbhe, Navi Mumbai, 400705, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Tawde
mesh_terms: D000279:Administration, Cutaneous; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D005782:Gels; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical
chemical_list: D005782:Gels; D004008:Diclofenac; D011092:Polyethylene Glycols; C000595213:polyethylene glycol 400
keywords: diclofenac sodium; gel; hot melt extrusion; kolliphor® P407; kollisolv® PEG 400; stability; texture analyzer