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Physicochemical characterization of naproxen microcrystals for colon specific pulsatile drug delivery designed using pulsincap technique

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Abstract

Colon targeted pulsatile drug delivery system of naproxen microcrystals (NMs) was developed using pulsincap technique in order to match release of drug with circadian rhythm of the clinical symptoms of rheumatoid arthritis. NMs were prepared by anti-solvent precipitation method using various solubilizers, viz, sodium lauryl sulfate (SLS), hydroxy propyl methyl cellulose (HPMC K4M), polyvinylpyrrolidone (PVP K-30) and polyethylene glycol (PEG 6000) in order to enhance solubility of drug. Solubility analysis revealed SLS and HPMC K4M as suitable solubilizers for improving solubility of drug. Thus, NMs embedded with same solubilizers at 0.01% w/w were subjected for further evaluation. Particle size, surface morphology, degree of crystallinity and purity were determined for NMs. Pulsincap formulations were prepared by incorporating granulates of NMs inside formaldehyde treated body of hard gelatin capsules which were plugged using HPMC K15M at various concentrations. Drug release studies were performed in simulated gastric, intestinal and colonic fluid for 2, 4 and 2.5 h respectively in a successive manner. In vitro release data revealed that a capsule containing 35 mg of HPMC K15M exhibited complete drug release after lag time of 6 h. HPMC K4M as superior solubility enhancer for naproxen in multi-particulate microcrystals was also revealed from release studies.

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Acknowledgements

The authors gratefully acknowledge Department of Pharmacy, Kathmandu University, Dhulikhel, Nepal for providing laboratory facilities. The authors are also thankful to Asian Pharmaceuticals Pvt. Ltd., Q.Med Formulations Pvt. Ltd. and Curex Pharmaceuticals Pvt. Ltd. for providing gift sample. The authors are also heartily thankful to National Academy of Science and Technology, Satdobato, Lalitpur, Nepal for conducting XRPD studies and Lab 102 Western Laboratory, Department of Materials and Metallurgical Engineering, Indian Institute of technology, Kalyanpur, UP, India for conducting SEM studies. This article does not contain any studies with human and animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Pharmacy, Kathmandu University, Dhulikhel, Nepal

    Rocky Thapaliya, Kailash Shrestha, Asmita Sharma, Neelam Dhakal, Pragya Manandhar & Sahana Shrestha

  2. Quest Pharmaceuticals Pvt. Ltd., Bara, Birgunj, Nepal

    Ravi Bhattarai

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  1. Rocky Thapaliya
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  2. Kailash Shrestha
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  3. Asmita Sharma
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  4. Neelam Dhakal
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  7. Ravi Bhattarai
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Correspondence to Ravi Bhattarai.

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Thapaliya, R., Shrestha, K., Sharma, A. et al. Physicochemical characterization of naproxen microcrystals for colon specific pulsatile drug delivery designed using pulsincap technique. J. Pharm. Investig. 49, 553–564 (2019). https://doi.org/10.1007/s40005-019-00425-3

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