Research Article Formulation Development of Rotigotine Transdermal System using Dot-Matrix Technology Shailesh T. Prajapati 1 , Vipulbhai Mandli 2* 1 Department of Pharmaceutics and Pharmaceutical Technology, Kalol Institute of Pharmacy, KIRC Campus, Ahmedabad-Mehsana Highway, Kalol-382721, Gandhinagar, Gujarat, India 2 Department of Pharmaceutical Sciences, Hemchandracharya North Gujarat University, Patan-384265, Gujarat, India Introduction A TDS is proposed to release the medicine into systemic circulation through skin to cure disorders in locations far away from the site of application. Exact shape and size of TDS are available for systemic action and are proposed for the treatment or prevention of systemic disease. Medicine released from the TDS is absorbed through skin into blood circulation and reached to target tissues to achieve a therapeutic effect. [1] TDS has many merits over conventional dosage forms; it will improves bioavailability, enhance therapeutic efficacy, avoid limitations of first-pass effect, and maintain steady plasma level of medicine. [2,3] Article history: Received: 07 May, 2020 Revised: 21 June, 2020 Accepted: 30 June, 2020 Published: 30 July, 2020 Keywords: Central composite design, Cold flow, Dot-matrix technology, Ex vivo skin permeation, Pressure-sensitive adhesive, Rotigotine. DOI: 10.25004/IJPSDR.2020.120414 The purpose of this research was to prepare and evaluate drug-in-adhesive type patches of rotigotine using dot-matrix technology, which is the new generation of drug-in-adhesive transdermal delivery system (TDS) that deliver drug therapy through less patch surface area and without compromising adhesion. Preformulation studies, like solubility in permeation enhancers, compatibility study, transmission study, uptake study, and crystallization study of rotigotine in various pressure-sensitive adhesive (PSA) polymers were performed. Transdermal system was prepared by solvent casting method. Central composite design (CCD) was chosen for optimization of the formulation. Design of experiment (DoE) was used to study the impact of critical formulation parameters, like silicone adhesive concentration, povidone K29/32 concentration, and propylene glycol concentration. Crystallization study of rotigotine in different PSAs suggested that crystal inhibitor is required to load drugs above 5%. Selection of optimum batch was made using a constraint-based graphical optimization technique. The optimum batch exhibited desired in vitro adhesion parameters, like peel, tack, shear, and permeation rate, which is suitable for 3 days’ wear properties and desired permeation rate. The optimum batch was evaluated for appearance, weight of matrix, thickness, % assay of drug content, in vitro adhesion testing, cold flow study, and ex vivo skin permeation studies. Backing film Scotchpak 9730 and release liner Scotchpak-1022 was selected based on transmission and uptake study of rotigotine. Stability study indicates that developed formulation remains stable. The present research confirms the feasibility of developing rotigotine transdermal system using novel technology. International Journal of Pharmaceutical Sciences and Drug Research 2020;12(4):404-414 Contents lists available at UGC-CARE International Journal of Pharmaceutical Sciences and Drug Research [ISSN: 0975-248X; CODEN (USA): IJPSPP] journal home page : http://ijpsdr.com/index.php/ijpsdr * Corresponding Author: Vipulbhai Mandli Address: Department of Pharmaceutical Sciences, Hemchandracharya North Gujarat University, Patan-384265, Gujarat, India Email : vipul_mandli@yahoo.com Tel.: +91-9898146888 Relevant conflicts of interest/financial disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Copyright © 2020 Shailesh T. Prajapati et al. This is an open access article distributed under the terms of the Creative Commons Attribution- NonCommercial-ShareAlike 4.0 International License which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. ABSTRACT ARTICLE INFO There are mainly two types of TDS, matrix type and reservoir type. Matrix type TDS contains drug in PSA, while reservoir type system may contain drug in solution or in PSA, but there is the rate-controlling membrane to manage the delivery of medicine. [4,5] Dot-matrix technique delivers the desired dose in low concentration and also reduces the size of the patch. Dot-matrix technique produces particles of drug-loaded polymer with very large surface area forming concentrated drug microcells in the polymer, which can hold a large amount of drug. This technique utilizes two polymers, i.e., acrylic polymer and silicone polymer. Firstly a highly concentrated drug solution is solubilized in acrylic polymer, and then the above solution