Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet.
The work was aimed at developing calcium-pectinate matrix tablet for colon-targeted delivery of meloxicam (MLX) microsponges. Modified quassi-emulsion solvent diffusion method was used to formulate microsponges (MS), based on 3(2) full factorial design. The effects of volume of dichloromethane and EudragitRS100 content (independent variables) were determined on the particle size, entrapment efficiency and %cumulative drug release of MS1-MS9. The optimized formulation, MS5 (d(mean)=44.47 μm, %EE=98.73, %CDR=97.32 and followed zero order release) was developed into colon-targeted matrix tablet using calcium pectinate as the matrix. The optimized colon-targeted tablet (MS5T2) shielded MLX loaded microsponges in gastrointestinal region and selectively delivered them to colon, as vizualized by vivo fluoroscopy in rabbits. The pharmacokinetic evaluation of MS5T2 in rabbits, revealed appearance of drug appeared in plasma after a lag time of 7h; a t(max) of 30 h with Fr=61.047%, thus presenting a formulation suitable for targeted colonic delivery. CLSM studies provided an evidence for colonic luminal retentive ability of microsponges at the end of 8h upon oral administration of MS5T2. Thus calcium pectinate matrix tablet loaded with MLX microsponges was developed as a promising system for the colon-specific delivery that has potential for use as an adjuvant therapy for colorectal cancer.
Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH#2, Mathura 281001, India.
Rishabh
R
Srivastava
Deepesh
D
Kumar
Kamla
K
Pathak
D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D004058:Diffusion; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients; D005471:Fluoroscopy; D000077239:Meloxicam; D010316:Particle Size; D010368:Pectins; D011817:Rabbits; D015203:Reproducibility of Results; D012212:Rheology; D012995:Solubility; D012997:Solvents; D013499:Surface Properties; D013607:Tablets; D013843:Thiazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D004655:Emulsions; D005079:Excipients; D012997:Solvents; D013607:Tablets; D013843:Thiazines; D013844:Thiazoles; D010368:Pectins; D000077239:Meloxicam