Sustained Release Bilayer Tablet of Ibuprofen and Phenylephrine Hydrochloride: Preparation and Pharmacokinetics in Beagle Dogs
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Cold is a global common infectious disease accompanied by symptoms such as headache and stuffy nose. Ibuprofen (IBU) and phenylephrine hydrochloride (PE) were commonly used for common cold due to their different effects in relieving fever and the main symptoms such as nasal congestion and high sinus pressure. However, the commercial tablets of IBU and PE have to be administered 2 to 3 times per day due to their short half-life, with inconvenience for patient and fluctuations of plasma concentration. Bilayer tablet technology was utilized to design the IBU-PE sustained release tablets because of the significantly different solubility of IBU and PE in release media. The formulations of IBU layer and PE layer contain different viscosity grades of hydroxypropyl methylcellulose (HPMC) as sustained-release matrix, hydrophilic diluent, and traditional glidant and lubricant. The sustained release bilayer tablet exhibited satisfying sustained release performance with the mechanisms of diffusion and matrix erosion. Compared with the conventional tablets, the IBU-PE sustained release bilayer tablet expressed significantly sustained-release behavior with decreased Cmax and prolonged Tmax in fasted conditions for IBU and PE. Though IBU of IBU-PE sustained release bilayer tablet was bioequivalent to the commercial IBU tablet, the relative bioavailability of PE from the bilayer tablets was 87.49 ± 20.00% (90% confidence interval was 72.3 to 102.5%), indicating bioinequivalence probably due to the “first pass” effect.
KEY WORDSibuprofen phenylephrine hydrochloride sustained release bilayer tablet pharmacokinetics bioavailability
This work was supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2017ZX09101001-004) and National Natural Science Funds for Young Scholar (81503011).
- 2.Adams PF, Hendershot GE, Marano MA. Current estimates from the National Health Interview Survey, 1996. Vital Health Stat. 1999;(200):1–203.Google Scholar
- 3.Hsiao J, Cherry D, Beatty P, Rechtsteiner E. National Ambulatory Medical Care Survey: 2007 summary. National health statistics report; no 27. Hyattsville, MD: National Center for Health Statistics; 2010.Google Scholar
- 9.Food AD. Over-the-counter drugs: establishment of a monograph for OTC cold, cough, allergy, bronchodilator and antiasthmatic products.[21 CFR 341]. Fed Regist. 1976;41:38399–400.Google Scholar
- 24.Wang HY, Kong AY, Yang B, Yan LP, Di X. Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC. Yao Xue Xue Bao. 2015;50(12):1607–12.Google Scholar
- 25.Gelotte CK, Zimmerman BA. Pharmacokinetics, safety, and cardiovascular tolerability of phenylephrine HCl 10, 20, and 30 mg after a single oral administration in healthy volunteers. Clin Drug Investig. 2015;35(9):547–58. https://doi.org/10.1007/s40261-015-0311-9.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Grund J, Korber M, Bodmeier R. Predictability of drug release from water-insoluble polymeric matrix tablets. Eur J Pharm Biopharm: 2013;85(3 Pt A):650–655. doi: https://doi.org/10.1016/j.ejpb.2013.08.007.
- 34.Tukaram BN, Rajagopalan IV, Shartchandra PSI. The effects of lactose, microcrystalline cellulose and dicalcium phosphate on swelling and erosion of compressed HPMC matrix tablets: texture analyzer. Iran J Pharm Res: IJPR. 2010;9(4):349.Google Scholar
- 36.Franek F, Fransson R, Thorn H, Backman P, Andersson PU, Tehler U. Ranking in vitro dissolution of inhaled micronized drug powders including a candidate drug with two different particle sizes. Mol Pharm. 2018;15(11):5319–26. https://doi.org/10.1021/acs.molpharmaceut.8b00796.CrossRefPubMedGoogle Scholar
- 40.Singhvi G, Singh M. Review: In-vitro drug release characterization models. Int J Pharm Sci Res. 2011;2(1):77–84.Google Scholar