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Inulin-Based Tablet in Capsule Device for Variable Multipulse Delivery of Aceclofenac: Optimization and In Vivo Roentgenography

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Abstract

The aim of the study was to develop single-unit tablet in capsule system of aceclofenac for the treatment of late night pain and morning stiffness associated with rheumatoid arthritis. The system was conceptualized as a three-component design (1) a hard gelatin enteric-coated capsule (for carrying two pulses), (2) first-pulse granules (for rapid release in intestine), and (2) second-pulse matrix tablet (for slow release in colon). An appropriate integration of pH-sensitive (Eudragit S100) and bacteria-responsive (inulin) functions, on the basis of 32 factorial design, led to formulation of TICS 1–9 that were screened for in vitro release. TICS 2 with biphasic drug release of 98.64% from first-pulse granules in simulated intestinal fluid (12 h) and 97.82% from second-pulse matrix tablet in simulated colonic fluid (24 h) was the optimized formulation that exhibited Fickian diffusion of drug (n = 0.363). In vivo fluoroscopy in rats traced the intact tablet to colon in 7.5 h that got eroded at the tenth hour. This demonstrated the colon-specific delivery of the matrix tablet affirming the potential of the system to obviate the need for two-time administration of drug at odd hours. The experimental design was validated by extra design check point, and diffuse reflectance spectroscopy and DSC revealed absence of chemical interaction between the formulation excipients.

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ACKNOWLEDGMENTS

The authors are thankful to Ranbaxy Research Laboratory, Gurgaon, India for providing aceclofenac as gift sample and to All India Council for Technical Education for providing final assistance to carry out research work. The authors are highly indebted to Prof Satish Kumar Garg, Dean, Pt. Deen Dayal Upadhayaya Veterinary University, Mathura, India for extending the facilities for in vivo roentgenography study.

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  1. Department of Pharmaceutics, Rajiv Academy for Pharmacy, P.O. Chattikara, Mathura, 281001, Uttar Pradesh, India

    Puja Sharma & Kamla Pathak

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  1. Puja Sharma
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  2. Kamla Pathak
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Correspondence to Kamla Pathak.

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Sharma, P., Pathak, K. Inulin-Based Tablet in Capsule Device for Variable Multipulse Delivery of Aceclofenac: Optimization and In Vivo Roentgenography. AAPS PharmSciTech 14, 736–747 (2013). https://doi.org/10.1208/s12249-013-9959-8

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