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. 2024 Jun 16;17(6):787.
doi: 10.3390/ph17060787.

In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations

Kyoung Ah Min  1 , Na Young Kim  2   3 , Min Jeong Jin  2   3 , Doyeon Kim  1 , Yoonseo Ma  2 , Sandeep Karna  2 , Young-Joon Park  2   3
Affiliations

In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations

Kyoung Ah Min et al. Pharmaceuticals (Basel). .

Abstract

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets.

Keywords: capsule; cilostazol; in vitro; in vivo; pharmacokinetics; release; two-period crossover design.

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Conflict of interest statement

Young-Joon Park is a current IMDpharm Inc. Employee. The company had a role in the design of the study but did not have a role in the collection, analysis, or interpretation of data, writing of the manuscript, or decision to publish the results.

Figures

Figure 1
Figure 1
In vitro release profiles of Pletaal® SR 200 mg capsules and Cilostan® CR 200 mg tablets at a paddle speed of 50 rpm. (A) Release medium pH 1.2 containing 0.5% SLS (paddle 50 rpm), (B) release medium pH 4.0 containing 0.5% SLS (paddle 50 rpm), (C) release medium pH 6.8 containing 0.5% SLS (paddle 50 rpm), and (D) release medium containing distilled water with 0.5% SLS (paddle 75 rpm).
Figure 2
Figure 2
In vitro release profiles of Pletaal® SR 200 mg capsules and Cilostan® CR 200 mg tablets with basket method at 100 rpm. (A) Pseudo gastric release medium transfer set up from pH 1.2 to pH 6.8 (+0.5% SLS), and (B) Pseudo gastric release medium transfer set up from pH 1.2 to pH 6.8 (+1.0% SLS).
Figure 3
Figure 3
In vitro release profiles of Pletaal® SR 200 mg capsules and Cilostan® CR 200 mg tablets with a paddle method at 50 rpm. (A) Release medium FeSSIF with paddle at 50 rpm, (B) telease medium FaSSIF with paddle at 50 rpm, and (C) telease medium FaSSGF with paddle methods at 50 rpm.
Figure 4
Figure 4
LC MS/MS chromatograms. (A) Domperidone (IS) internal standard at 1 ng/mL, (B) Cilostazol in blank beagle plasma spiked with known drug concentrations 1 ng/mL of Cilostazol along with IS 1 ng/mL of Domperidone, (C) Cilostazol in blank beagle plasma spiked with 10 ng/mL of Cilostazol along with 1 ng/mL of IS, (D) OPC-13015 in blank beagle plasma spiked with known drug concentrations 1 ng/mL of OPC-13015 along with IS 1 ng/mL of Domperidone, (E) OPC-13015 in blank beagle plasma spiked with 10 ng/mL of OPC-13015 along with 1 ng/mL of IS, (F) OPC-13212 in blank beagle plasma spiked with known drug concentrations 1 ng/mL of OPC-13212 along with IS 1 ng/mL of Domperidone, and (G) OPC-13212 in blank beagle plasma spiked with 10 ng/mL of OPC-13212 along with 1 ng/mL of IS. ** The transmission ion to a product ion.
Figure 4
Figure 4
LC MS/MS chromatograms. (A) Domperidone (IS) internal standard at 1 ng/mL, (B) Cilostazol in blank beagle plasma spiked with known drug concentrations 1 ng/mL of Cilostazol along with IS 1 ng/mL of Domperidone, (C) Cilostazol in blank beagle plasma spiked with 10 ng/mL of Cilostazol along with 1 ng/mL of IS, (D) OPC-13015 in blank beagle plasma spiked with known drug concentrations 1 ng/mL of OPC-13015 along with IS 1 ng/mL of Domperidone, (E) OPC-13015 in blank beagle plasma spiked with 10 ng/mL of OPC-13015 along with 1 ng/mL of IS, (F) OPC-13212 in blank beagle plasma spiked with known drug concentrations 1 ng/mL of OPC-13212 along with IS 1 ng/mL of Domperidone, and (G) OPC-13212 in blank beagle plasma spiked with 10 ng/mL of OPC-13212 along with 1 ng/mL of IS. ** The transmission ion to a product ion.
Figure 5
Figure 5
Plasma concentration vs. time profile of Cilostazol, OPC-13015, OPC-13213 in beagle dog plasma. (A) Fast and (B) feed conditions after a single oral administration of Pletaal® SR 200 mg capsule or Cilostan® CR 200 mg tablet.
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References

    1. Tanaka T., Ishikawa T., Hagiwara M., Onoda K., Itoh H., Hidaka H. Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle. Pharmacology. 1988;36:313–320. doi: 10.1159/000138400. - DOI - PubMed
    1. Reilly M.P., Mohler E.R., III Cilostazol: Treatment of intermittent claudication. Ann. Pharmacother. 2001;35:48–56. doi: 10.1345/aph.19408. - DOI - PubMed
    1. Pearce L., Ghosh J., Counsell A., Serracino-Inglott F. Cilostazol and peripheral arterial disease. Expert Opin. Pharmacother. 2008;9:2683–2690. doi: 10.1517/14656566.9.15.2683. - DOI - PubMed
    1. Liu Y., Shakur Y., Yoshitake M., Kambayashi J.i. Cilostazol (Pletal®): A dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc. Drug Rev. 2001;19:369–386. doi: 10.1111/j.1527-3466.2001.tb00076.x. - DOI - PubMed
    1. Eikelboom J.W., Hirsh J., Spencer F.A., Baglin T.P., Weitz J.I. Antiplatelet drugs: Antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e89S–e119S. doi: 10.1378/chest.11-2293. - DOI - PMC - PubMed