Development and optimization of sustained release mucoadhesive composite beads for colon targeting

• Published in: International journal of biological macromolecules 2019-10, Vol.139, p.320-331
• Main Authors: Kurra, Pallavi, Narra, Kishore, Puttugunta, Srinivasa Babu, Kilaru, Naveen Babu, Mandava, Basaveswara Rao
• Format: Article
• Language: English
• Subjects: Alginates - chemistry; Capecitabine; Chemistry, Pharmaceutical; Colon - drug effects; Delayed-Action Preparations; Drug Carriers - chemistry; Drug Liberation; Flax - chemistry; Gastrointestinal Microbiome; Hibiscus leaf gum; Intestinal Mucosa - drug effects; Kinetics; Linum seed mucilage; Microspheres; Pectins - chemistry; Plant Gums - chemistry; Plant Mucilage - chemistry; Seeds - chemistry; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; Tissue Adhesions
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.07.190

The present work investigates a blend of Linum Seed mucilage(LSM) and Hibiscus Leaf gum(HLG) as mucoadhesive carriers for Capecitabine(CPTB) loaded mucoadhesive composite bead formulation (CMB), in an attempt to achieve sustained release of CPTB (BCS Class I drug) in the colon region. Optimization using Box-Behnken Design(BBD) was used to study the effect of quantities of mucoadhesive carriers(LSM,HLG) and enteric polymer pectin (in curing solution) on response factors such as %drug loading (%DL) and %drug release (%DR). CMB prepared by ion-gelation technique showed uniform bead size, spherical surface morphology, maximum drug encapsulation efficiency. The optimized CMB(F18) exhibited maximum %drug loading(28.94%), favorable in vitro drug release of CPTB(54.43%) in 12 h, where, the release kinetics follow zero order non-Fickian diffusion mechanism. CMB's exhibited significantly higher swelling upon exposure to alkaline media than acidic media similarly ex vivo mucoadhesive study also revealed that major fraction of beads were washed off within 2 h in 1.2pH media whereas in 7.4pH alkaline media major portion of the beads remain adhered even after 24 h Moreover accelerated stability testing of CMB(F18) revealed shelf life of about 2.59 years. Hence the study confirms that the combination of LSM&HLG as ideal mucoadhesive carriers and can favorably target highly soluble drugs to the colon region. [Display omitted] •Linum Seed Mucilage (LSM) and Hibiscus Leaf Gum (HLG) were exploited as potent biomaterials for mucoadhesive drug delivery.•A novel formulation of capecitabine (CPTB) loaded LSM:HLG-Pectin mucoadhesive composite beads was developed.•Maximum drug loading and relevant sustained drug release pattern of freely wáter soluble drug (CPTB) was achieved via optimized mucoadhesive composite bead formulation.•Optimized CPTB loaded composite bead formulation favourably targeted drug to the colon región.