Original Article FORMULATION AND OPTIMIZATION OF BUDESONIDE COLON-TARGETED TABLETS USING CONTROLLED POROSITY OSMOTIC PUMP TECHNOLOGY VOLETI VIJAYA KUMAR , ISMAIL Y. * Crescent School of Pharmacy, B. S. Abdur Rahman Crescent Institute of Science and Technology, GST Road, Vandalur, Chennai-600048, Tamil Nadu, India * Corresponding author: Ismail Y.; * Email: ismailcsp@crescent.education Received: 01 Sep 2024, Revised and Accepted: 15 Nov 2024 ABSTRACT Objective: Formulation and optimization of Budesonide (BDU) controlled porosity osmotic pump tablets (CPOP) to treat Nocturnal Asthma (NA) by adopting the Quality by design approach was set as objective of this research work. Methods: Solubility of Budesonide was enhanced by converting in to the form of BUD Solid dispersions, using poloxamer 188. Controlled Porosity Osmotic pump (CPOP) tablets of budesonide were formulated by wet granulation technique. Quality by design approach using Box-Behnken design was adopted to optimize the selected critical factors. The optimized formulation was compared with the marketed extended-release formulation. Results: The percentage of drug released at 4 h (D4), 7 h (D7), and 10 h (D10) were identified as response factors during the optimization phase. Statistical analysis showed that a combination of 200 mg of the SPM coat, 19.72 mg of Eudragit S 100 for the enteric coating, and 69.74 mg of guar gum in the core could achieve drug release rates of 9.4% after 4 h, 55.9% after 7 h, and 96.6% after 10 h of administration for the CPOP tablets. Conclusion: The results indicated that the CPOP tablets were successfully formulated for colon-targeted drug release. Keywords: Design of experiments, CPOP tablets, Box-behnken design, ANOVA test, Enteric coating, Semipermeable membrane, Polysaccharides © 2025 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.2025v17i1.52544 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Asthma is a chronic disorder in many people across the globe. There have been numerous studies on asthma concluding the symptoms got worsen in the night during sleep. This kind of asthma is called as ‘nocturnal asthma (NA)’. According to National Heart, Lung and Blood Institute (NHLBI, A branch of National Institute of Health, USA), the lung function because of NA becomes worsen in the night with increased symptoms and airway resistance, thus requiring medication at that time [1]. Asthmatic attacks are less common in the first half of night. The air-way resistance increases progressively through the night and much greater during the sleep [2, 3]. Hence, this chronopathology of NA suggests that administration of anti- asthmatic drugs that are developed based on Chrono pharmaceutical technology is most desirable in consideration of the patient convenience. This can be achieved only through formulating Colon Targeting Drug Delivery Systems (CTDDS). These systems are formulated such that they prevent the drug release in the upper GIT and allow the drug to release only after crossing the ileocecal valve that connects the ileum to colon. After administration, passage of intact solid dosage form to the colon generally requires around 6-8 h (around 2-3 h to cross stomach and around 4-5 h to cross small intestine). Administration of these solid CTDDS after night meal at around 9 pm can produce the dosage form in the colon at around 4 am in the next day morning. So, the immediate release of any anti- asthmatic drug loaded can produce the desired plasma concentration at the most needed time to prevent the early morning attacks of asthma. Budesonide (BUD) is one of the treatment options to treat patients with mild to moderate asthma symptoms. Budesonide belongs to the class of corticosteroids acts as bronchodilator to relieve the pain and inflammation associated with asthma attacks [4, 5]. Budesonide has high first-pass metabolism (around 90% of the dose) form the upper GIT resulting absorption of only around 10% of the administered dose. In contrast, this drug exhibited significantly high absorption around 60-80% from the ileum and colon [6, 7]. Further, it is well evidenced that budesonide can cause bleeding in the upper GIT [8] which is asymptomatic and can be discovered only when serious hemorrhage occurs. These facts suggest that it is of great necessity for Budesonide to be released only in the lower GIT i. e. in the ileum and colon for better absorption as well as preventing GI bleeding. Hence, this drug is also best-suitable for developing into CTDDS. As per literature BUD belongs to the class-II of Biopharmaceutical classification system (BCS), which is characterized by poor solubility and high permeability [9]. Such type of APIs exhibits dissolution limited bioavailability. As the current study focusing on the targeted drug release site is colon [10, 11], and by considering the less availability of fluids in colon, it is necessary to improve the solubility of BUD. Different approaches are available in the literature to improve the solubility of the drugs; among all the approaches, solid dispersion was found to have various advantages like ease of preparation, reduced cost for preparation, improve wettability. Osmotic drug delivery systems are the most promising drug delivery systems with controlled drug release manner with aid of osmotic pressure [12]. Controlled Porosity Osmotic Pumps (CPOP) is one of the most dependable osmotic drug delivery systems to have desired drug release for the diseases associated with circadian rhythms like asthma [13] CPOP systems have unique advantage over conventional osmotic systems that they don’t need mechanical drilling of orifice on the semipermeable membrane (SPM) for drug release. Instead, the SPM contains a substance that is dissolved/eroded/degraded in the favorable conditions upon administration and provide numerous micropores to allow the drug release [14, 15]. Use of natural polysaccharides like chitosan and guar gum gained an advantage because of its gelling property. These polysaccharides are degraded by the enzymes of colonic microflora once reaches to the colonic region. Present research consisted of enhancing solubility of the BUD by solid dispersions, developing CPOP tablets with polysaccharides and coating them with enteric polymers to so as to minimize the drug release in the upper GIT and achieving the targeted release in the lower GIT. Quality by design (QbD) [16] was applied to study the influence of several factors on the drug release form the CPOP tablets also to optimize the formulation towards achieving the desired drug release profile. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 17, Issue 1, 2025