FORMULATION OF MESALAMINE-LOADED RECTAL MUCOADHESIVE PELLETS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE USING 3 2 FULL FACTORIAL DESIGN Original Article PAYAL N. VAJA * , CHETAN M. DETROJA Department of Pharmaceutics, School of Pharmacy, R. K. University, Rajkot, Gujarat 360020, India Email: payalvaja55@gmail.com Received: 12 May 2022, Revised and Accepted: 15 Jun 2022 ABSTRACT Objective: The objective of the present work was to optimize a rectal suppository containing mucoadhesive pellets of Mesalamine to achieve local yet sustained release of Mesalamine for once-a-day administration for the therapy of Inflammatory Bowel Disease. Methods: Thus, the present work involves forming mucoadhesive pellets of mesalamine by extrusion spheronization, which were then loaded into a suppository to be administered rectally. The pellets were evaluated for mucoadhesion strength, swelling potential, morphology, particle size, drug release, drug loading and retention time. Results: The optimized batch of pellets using Eudragit RLPO as the release retardant, carrageenan as a mucoadhesive polymer and other excipients had a mucoadhesion strength of 0.143 N, a swelling index of 50.50 %, and 44 % and 75 % drug was released from them at the end of 6 and 15 h respectively. The pellets-loaded cocoa butter suppositories had a melting range of 35–37 °C, disintegrated within 8–9 min and had a hardness of 4–5 kg/cm 3 . A comparison of the in vitro drug release profile from the mucoadhesive pellets and the mucoadhesive pellets-loaded suppositories showed a closeness in the % cumulative drug release indicating that cocoa butter did not interfere in the release of the drug from the pellets. Conclusion: Mucoadhesive Pellets were successfully developed by extrusion spheronizer technique and incorporated into suppositories. In vitro study revealed a release profile that warranted a once-a-day regimen leading to a reduction in the requirement of the drug and hence the side effects. Keywords: Inflammatory bowel disease, Extrusion, Spheronization, Suppository, Sustained release, Mucoadhesion © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022v14i5.45180. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Inflammatory Bowel Disease (IBD) are various chronic and relapsing inflammatory conditions in which the body's immunity framework assaults the parts of the digestive system [1]. IBD is partitioned into two conditions, Crohn's disease (CD) and ulcerative colitis (UC), which are impacted by ongoing inflammation of the gastrointestinal tract (GIT) [2]. There is no absolute remedy for IBD; exceptions to that are the medicines responsible for lessening and controlling the indications of the disease. In CD, irritation can happen in any segment of the GIT, yet it most often influences the terminal section of the small intestine and the initial length of the large intestine. In the case of UC, aggravation primarily occurs in the innermost lining of the colon and the rectum. The exact cause of IBD is obscure; however, IBD is the consequence of an imperfect immune system. An appropriately working immune system assaults unfamiliar organic entities, for example, infections and microorganisms, to secure the body. However, on account of IBD, the immune system botches innocuous substances in the digestive system as foreign and dispatches an assault, bringing about inflammation. A mix of four elements is purported to cause IBD, viz, hereditary elements like enhanced intestinal permeability, natural factors, an irregularity of GI microflora, and an improper response from the immunity apparatus [3]. Manifestations of IBD are fever, loss of hunger, weight reduction, sluggishness, late evening perspiring, development impediment and amenorrhea [4]. Mesalamine (MSL) is the first-line choice in the treatment of mild-to- moderate UC [5, 6]. It has multiple anti-inflammatory actions that include inhibiting leukotrienes and Interleukin-1 production, lessening mucosal inflammation by acting on mucosal colonic epithelial cells, and acting as a free radical scavenger [7]. Although effective orally, the treatment is plagued by serious adverse reactions such as allergic reactions, pancreatitis, hepatotoxicity, bone marrow suppression, interstitial nephritis, and haemolytic anemia or megaloblastic anemia. All of these could be attributed to the systemic absorption and the non-specific distribution of the drug [8]. Thereby there is a need to find an alternative to the oral administration of MSL. One such solution could be the rectal delivery of the drug under consideration. This would provide benefits like targeted action, a quicker response time and a reduction in the frequency of dosing. Studies have suggested that topical preparations result in better responses and a quicker improvement in the case of mild-to-moderate distal UC when compared with oral therapy. The rectal delivery of 5–aminosalicylic acid led to its mucosal concentration being 200-fold higher than that could be achieved by oral administration alone [9]. Rectal preparations range from conventional enemas and suppositories to novel formulations like sustained release multiparticulates that could be incorporated into the conventional forms to reap the benefits of both the traditional and modern formulations. Multiparticulates are the discrete, small and repetitive units of drug particles that may or may not possess similar drug release profiles. They could be programmed to provide a delayed, controlled or pulsatile drug release pattern. They have a distinct benefit, owing to their small size, generally less than 200 µm, they are not affected by the variations in the gastric and intestinal transit time and would reach the target site, i.e., the colon, quickly [10]. On account of the same consideration, they would house in the ascending colon for a longer period as compared to a large, single unit dosage form. The success of the therapy depends not only on the swiftness with which the drug reaches the intended target site but also on the duration for which it resides in the said location. One such account of increasing the residence time of any formulation is the incorporation of mucoadhesive polymers, which would prolong the time for which the dosage form stays in the colon [11]. A lot of research is being focussed on using natural polymers for formulation development due to their natural biodegradability, thus, carrageenan would be used as the polymer to formulate mucoadhesive pellets [12]. Thus, the objective of the present work was to optimize a rectal suppository containing mucoadhesive pellets of MSL to achieve local İD İD International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 14, Issue 5, 2022