title: In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.
abstract: Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan, Amman, Jordan. abjaber@ju.edu.jo.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bani-Jaber
authors.affiliation: Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Al-Isra University, Amman, Jordan.
authors.forename: Iyad
authors.initials: I
authors.lastname: Alshawabkeh
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Samaa
authors.initials: S
authors.lastname: Abdullah
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
authors.forename: Imad
authors.initials: I
authors.lastname: Hamdan
authors.affiliation: Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
authors.forename: Adel
authors.initials: A
authors.lastname: Ardakani
authors.affiliation: Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
authors.forename: Maha
authors.initials: M
authors.lastname: Habash
mesh_terms: D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002364:Caseins / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010434:Pepsin A / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014357:Trypsin / Q000032:analysis / Q000378:metabolism*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002364:Caseins; D004337:Drug Carriers; D014357:Trypsin; D010434:Pepsin A
keywords: bioavailability; casein; dissolution; mefenamic acid; solid dispersions