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

  • Rocky Thapaliya
  • Kailash Shrestha
  • Asmita Sharma
  • Neelam Dhakal
  • Pragya Manandhar
  • Sahana Shrestha
  • Ravi BhattaraiEmail author
Original Article


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.


Anti-solvent precipitation Chrono-therapeutic Microcrystals Pulsincap Rheumatoid arthritis 



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.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest with the contents of this article.


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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  • Rocky Thapaliya
    • 1
  • Kailash Shrestha
    • 1
  • Asmita Sharma
    • 1
  • Neelam Dhakal
    • 1
  • Pragya Manandhar
    • 1
  • Sahana Shrestha
    • 1
  • Ravi Bhattarai
    • 2
    Email author
  1. 1.Department of PharmacyKathmandu UniversityDhulikhelNepal
  2. 2.Quest Pharmaceuticals Pvt. Ltd.BirgunjNepal

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