Double controlled release of highly insoluble cilostazol using surfactant-driven pH dependent and pH-independent polymeric blends and in vivo bioavailability in beagle dogs

[Display omitted] Commercially available cilostazol (CIL) tablet releases drug immediately and is given twice a day as an antiplatelet and vasodilatory agent. However, clinical usefulness of immediate release (IR) preparation is limited due to its extremely poor water solubility and the difficulty i...

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Bibliographic Details
Published in:International journal of pharmaceutics 2019-03, Vol.558, p.284-290
Main Authors: Nam, Kyu-Yeol, Cho, Sang Min, Choi, Youn-Woong, Park, Chulhun, Meghani, Nileshkumar M., Park, Jun-Bom, Lee, Beom-Jin
Format: Article
Language:English
Subjects:
Binary polymeric blend
Cilostazol
Double controlled-release matrix tablet
Enhanced dissolution
Patient centricity
Poorly water-soluble drug
Surfactant-driven modulation
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Summary:[Display omitted] Commercially available cilostazol (CIL) tablet releases drug immediately and is given twice a day as an antiplatelet and vasodilatory agent. However, clinical usefulness of immediate release (IR) preparation is limited due to its extremely poor water solubility and the difficulty in sustaining the blood concentration, resulting in unwanted side effects such as headaches, pyknocardia and heavy-headed symptoms. To achieve once a day dosage form with enhanced solubility and controlled release, double controlled release CIL matrix tablets (DCRT) were designed by modulating a sol–gel process of binary polymeric blends of a pH-independent hydroxylpropylmethylcellulose (HPMC) and a pH-dependent polymer (carbomer) assisted with anionic surfactant (sodium lauryl sulfate, SLS). The release profiles of the DCRT were varied according to the ratio of the two polymers. This DCRT enhanced dissolution rate of CIL in a controlled manner due to the sol–gel and erosion process of HPMC, and SLS-driven modulation of charged carbomer via neutralization and micellar interaction. The near-infrared (NIR) chemical imaging and gravimetric behaviors of DCRT clearly showed dynamic modulation of CIL during the swelling and hydration process. Furthermore, the plasma concentration of CIL in DCRT was highly improved and sustained in beagle dogs in a controlled manner.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2019.01.004