_____________________________________________________________________________________________________ # Associate Professor, *Corresponding author: E-mail: prasanthidhanu@gmail.com; Journal of Pharmaceutical Research International 34(40A): 29-43, 2022; Article no.JPRI.87819 ISSN: 2456-9119 (Past name: British Journal of Pharmaceutical Research, Past ISSN: 2231-2919, NLM ID: 101631759) Pulsatile Delivery of Methylphenidate Hydrochloride Pulsincap by Box-Behnken Design S. Ramadevi a , Javeria Tamkeen a , Aisha Rahman a and D. Prasanthi a#* a Department of Pharmaceutics, G. Pulla Reddy College of Pharmacy, Mehdipatnam, Hyderabad, Telangana, 500028, India. Authors’ contributions This work was carried out in collaboration among all authors. All authors read and approved the final manuscript. Article Information DOI: 10.9734/JPRI/2022/v34i40A36254 Open Peer Review History: This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers, peer review comments, different versions of the manuscript, comments of the editors, etc are available here: https://www.sdiarticle5.com/review-history/87819 Received 22 March 2022 Accepted 01 June 2022 Published 04 June 2022 ABSTRACT The objective of this study was to prepare and evaluate Methylphenidate hydrochloride pulsatile drug delivery system using pulsincap technique by applying Box-Behnken design. The drug is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD). Pulsincap system was prepared by using formaldehyde cross linked capsules. Capsules were filled with methylphenidate hydrochloride granules and hydrogel plug made of HPMC K100M is placed over granules to achieve desired drug release after lag time. The untreated cap was then fitted and sealed using 5% ethyl cellulose ethanolic solution to the formaldehyde treated capsule body. Granules were prepared by wet granulation technique using two polymers Ethyl cellulose and Eudragit RS100. Box-Behnken design was applied for optimization in which three independent variables, X1 = Drug: polymer ratio, X2 = Polymer: polymer ratio (Ethyl cellulose: Eudragit RS 100) and X3 = Plug weight were selected. Two dependent variables Y1 = lag time and Y2 = percent release were selected. The empty formaldehyde treated capsules were evaluated for physical appearance, solubility, capsule dimensions and formaldehyde content. Hydrogel plugs were evaluated for hardness & thickness of the plug, lag time and swelling index. Granules were evaluated for percentage yield, assay and flow properties. The prepared pulsincap formulations were evaluated for weight variation, content uniformity, capsule lock length, in-vitro dissolutions studies, drug kinetics and stability studies. Contour plots and Response surface plots indicated that with the increase in X1 and X3 there is increase in Lag time and decrease in % Original Research Article