Dissolution is an important preceding step for the absorption of drugs in class II of the Biopharmaceutics Classification System (BCS) resulting in poor bioavailability. This current study was directed at determining the outcome of in situ micronization technique on the dissolution and solubility profiles of paracetamol. Six formulations of paracetamol microcrystals were produced by the solvent change method using HPMC and PVP K30 as stabilizing agents. The solubility, percentage drug content, and dissolution patterns of the produced microcrystals were all tested. The study disclosed that paracetamol solubility was increased up to 5-fold in the PVP K30 stabilized paracetamol microcrystal and a 4.5-fold increase for HPMC stabilized paracetamol microcrystal. The time course of dissolution was improved significantly from 0.6%/min for plain paracetamol to 1.1%/min and 1.2%/min for HPMC and PVP K30 stabilized paracetamol microcrystal respectively. Formulation P6, with 0.08 g of PVP K30 as stabilizing agents and an anti-solvent to solvent ratio of 1:6 was the optimized formulation having a 5-fold solubility increase, 98.3% content of active and 95.32% drug release in 60 minutes. The solvent change strategy of the in situ micronization technique could be used for the augmentation of solubility and dissolution of paracetamol.
S. Weyler, F. Fulle, M. Diekmann, B. Schumacher, S. Hinz, K. Klotz, and C. Muller. ChemMedChem, 1 (8):
891-902(August 2006)Weyler, Stefanie Fulle, Friederike Diekmann, Martina Schumacher,
Britta Hinz, Sonja Klotz, Karl-Norbert Muller, Christa E Research
Support, Non-U.S. Gov't Germany ChemMedChem ChemMedChem. 2006 Aug;1(8):891-902..
R. Sauer, J. Maurinsh, U. Reith, F. Fulle, K. Klotz, and C. Muller. J Med Chem, 43 (3):
440-8(February 2000)Sauer, R Maurinsh, J Reith, U Fulle, F Klotz, K N Muller, C E In
Vitro Research Support, Non-U.S. Gov't United states Journal of medicinal
chemistry J Med Chem. 2000 Feb 10;43(3):440-8..
C. Muller, J. Sandoval-Ramirez, U. Schobert, U. Geis, W. Frobenius, and K. Klotz. Bioorg Med Chem, 6 (6):
707-19(June 1998)Muller, C E Sandoval-Ramirez, J Schobert, U Geis, U Frobenius, W
Klotz, K N England Bioorganic & medicinal chemistry Bioorg Med Chem.
1998 Jun;6(6):707-19..
M. Lohse, B. Elger, J. Lindenborn-Fotinos, K. Klotz, and U. Schwabe. Naunyn Schmiedebergs Arch Pharmacol, 337 (1):
64-8(January 1988)Lohse, M J Elger, B Lindenborn-Fotinos, J Klotz, K N Schwabe, U Germany,
west Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs
Arch Pharmacol. 1988 Jan;337(1):64-8..
R. Koch, A. Deger, H. Jack, K. Klotz, D. Schenzle, H. Kramer, S. Kelm, G. Muller, R. Rapp, and U. Weber. Eur J Biochem, 154 (2):
281-7(January 1986)Koch, R Deger, A Jack, H M Klotz, K N Schenzle, D Kramer, H Kelm,
S Muller, G Rapp, R Weber, U Comparative Study Research Support,
Non-U.S. Gov't Germany, west European journal of biochemistry / FEBS
Eur J Biochem. 1986 Jan 15;154(2):281-7..
K. Klotz, K. Krotec, J. Gripentrog, and A. Jesaitis. J Immunol, 152 (2):
801-10(January 1994)Klotz, K N Krotec, K L Gripentrog, J Jesaitis, A J R01-AI-22735/AI/NIAID
NIH HHS/United States In Vitro Research Support, Non-U.S. Gov't Research
Support, U.S. Gov't, P.H.S. United states Journal of immunology (Baltimore,
Md. : 1950) J Immunol. 1994 Jan 15;152(2):801-10..
K. Klotz, R. Keil, F. Zimmer, and U. Schwabe. J Neurochem, 54 (6):
1988-94(June 1990)Klotz, K N Keil, R Zimmer, F J Schwabe, U Research Support, Non-U.S.
Gov't United states Journal of neurochemistry J Neurochem. 1990 Jun;54(6):1988-94..
S. Hess, C. Muller, W. Frobenius, U. Reith, K. Klotz, and K. Eger. J Med Chem, 43 (24):
4636-46(November 2000)Hess, S Muller, C E Frobenius, W Reith, U Klotz, K N Eger, K In Vitro
Research Support, Non-U.S. Gov't United States Journal of medicinal
chemistry J Med Chem. 2000 Nov 30;43(24):4636-46..
G. Gimpl, R. Gerstberger, U. Mauss, K. Klotz, and R. Lang. J Biol Chem, 265 (30):
18142-7(October 1990)Gimpl, G Gerstberger, R Mauss, U Klotz, K N Lang, R E Research Support,
Non-U.S. Gov't United states The Journal of biological chemistry
J Biol Chem. 1990 Oct 25;265(30):18142-7..