679 Acta Poloniae Pharmaceutica – Drug Research, Vol. 78 No. 5 pp. 679–691, 2021 DOI: 10.32383/appdr/144132 Received 5 August 2021, Received in revised form 15 November 2021, Accepted 22 November 2021 PHARMACEUTICAL TECHNOLOGY FABRICATION AND CHARACTERIZATION OF MINOCYCLINE LOADED CHITOSAN MICROSPHERES BY CENTRAL COMPOSITE DESIGN FOR THE LOCAL DELIVERY IN PERIODONTAL POCKETS SHAMAMA JAVED 1 , WAQUAR AHSAN 2 *, SUSHAMA TALEGAONKAR 3 , and FARHAN J. AHMAD 3 1 Department of Pharmaceutics, College of Pharmacy, Jazan University, P. Box No. 114, Jazan, Saudi Arabia 2 Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, P. Box No. 114, Jazan, Saudi Arabia 3 Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi- 110062, India Abstract: This study was aimed to prepare, optimize and characterize cost-effective and mucoadhesive dental minocycline microspheres for the treatment of periodontitis. There is a need and scope for a cost- effective novel formulation of minocycline for periodontitis that can be delivered to the base of the pock- ets and is biodegradable, bioadhesive, and non-toxic. The Central composite design (CCD) was utilized to study the effects of process variables (5 levels) on the responses including size (R1), drug-entrapment (R2), mucoadhesion (R3), and percent in-vitro drug release (R4). Chitosan-minocycline microspheres were prepared by W/O emulsion technique using glutaraldehyde and sodium tripolyphosphate as differ- ent cross-linking agents. Results indicated that the concentration of polymer, drug, cross-linking agent, and cross-linking method signifcantly affected drug incorporation effciencies and microsphere charac- teristics. The minocycline release from the microspheres provided a retarded release up to 8 h and all concentrations were observed to be more than the minimum inhibitory concentration (MIC) required for inhibiting the growth of Staphylococcus aureus. The study concluded that the microspherical system pro- vides advantages over systemic drug administration, including reduction of systemic side effects and dra- matic increase in sustained drug concentrations in the gingival cervicular fuid. Local delivery by means of microspheres has several advantages over systemic drug intake including lesser systemic side effects, reduction of dose, mucoadhesiveness, and cost-effectiveness. Keywords: periodontitis, minocycline HCl, microspheres, chemically crosslinked, ionic gelation method, bioadhesion, Central composite design * Corresponding author: e-mail: wmohammad@jazanu.edu.sa Periodontitis is an infectious dental disease that causes breakdown of periodontal structures, attach- ment loss, and destruction of alveolar bone. A mouth rinse, subgingival irrigation, scaling and root plan- ning, systemic drug delivery, local sustained and controlled drug delivery constitute the non-surgical treatment modalities for it (1). Existing local drug delivery systems for periodontitis are often unsatis- factory as they are either nondegradable and the pa- tient must return for their removal, or degrade too slowly compared to the rapid drug release causing irritation to the periodontal pocket (2). It is therefore desirable to develop a biodegradable local drug-de- livery system that should simultaneously erode and release its drug so that the device disappears at the end of the releasing period, thereby eliminating the need for reapplication or device removal. This would enhance patient compliance and maintain a localized, effective drug concentration at the site of infection for a predetermined duration (3). Minocycline is the drug of choice in periodon- titis owing to several reasons including a broad spec- trum of activity, anti-collagenase activity, higher lipid solubility, high substantivity property, and rap- id uptake in human gingival fbroblasts (4). Dental flms, strips, ointments/gel/pastes, and micropar- ticulate/nanoparticulate systems of minocycline are available. The most popular commercial product is ARESTIN ® (1 mg, minocycline HCl microspheres) as an adjunct to the SRP procedure for reduction of periodontal pocket depth in patients with adult peri- odontitis (5). High ARESTIN ® treatment cost can ISSN 2353-5288 Polish Pharmaceutical Society