title: Incorporation of acetaminophen as an active pharmaceutical ingredient into porous lactose.
abstract: A new formulation method for solid dosage forms with drug loadings from 0.65 ± 0.03% to 39 ± 1% (w/w) of acetaminophen (APAP) as a model drug has been presented. The proposed method involves the production of highly-porous lactose with a BET surface area of 20 ± 1 m(2)/g as an excipient using a templating method and the incorporation of drug into the porous structure by adsorption from a solution of the drug in ethanol. Drug deposition inside the carrier particles, rather than being physically distributed between them, eliminated the potential drug/carrier segregation, which resulted in excellent blend uniformities with relative standard deviations of less than 3.5% for all drug formulations. The results of DSC and XRD tests have shown deposition of nanocrystals of APAP inside the nanopores of lactose due the nanoconfinement phenomenon. FTIR spectroscopy has revealed no interaction between the adsorbed drug and the surface of lactose. The final loaded lactose particles had large BET surface areas and high porosities, which significantly increased the crushing strengths of the produced tablets. In vitro release studies in phosphate buffer (pH 5.8) have shown an acceptable delivery performance of 85% APAP release within 7 minutes for loaded powders filled in gelatin capsules.
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia. Electronic address: amirali.ebrahimighadi@sydney.edu.au.
authors.forename: Amirali
authors.initials: A
authors.lastname: Ebrahimi
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia.
authors.forename: Morteza
authors.initials: M
authors.lastname: Saffari
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia.
authors.forename: Fariba
authors.initials: F
authors.lastname: Dehghani
authors.affiliation: School of Chemical & Biomolecular Engineering, Building J01, The University of Sydney, Darlington, NSW 2006, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Langrish
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005780:Gelatin; D007785:Lactose / Q000737:chemistry*; D053758:Nanoparticles; D016062:Porosity; D011208:Powders; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D002214:Capsules; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D013607:Tablets; D000082:Acetaminophen; D005780:Gelatin; D007785:Lactose
keywords: Acetaminophen; Content uniformity; Drug loading; Nanoconfinement; Porous lactose; Spray drying