In a previous study 1) we performed a comparative analysis of the properties of Cellactose, a coprocessed excipient for direct compression, and of two cellulose-lactose excipients (prepared by dry granulation and extrusion-spheronization respectively) of similar composition and particle size. We found major differences among the three excipients in particle structure and rheological properties, and in the mechanical properties and disintegration behaviour of the corresponding tablets.In the present study, as a follow-up to our previous study, 1) we evaluate the drug-loading capacities of these three excipients, since drug loading is one of the major limitations of excipients of this type.2) The model drugs used were acetaminophen (which is problematic at the compression stage 3,4) ) and furosemide (which is highly cohesive 5) ). Drug-loading capacity was evaluated in terms of the flow and compression properties of different drug-excipient mixtures, and the mechanical, microstructural and drug release properties of tablets prepared from these mixtures.
ExperimentalMaterials Cellactose, from Meggle, was supplied by Fher, S.A. (lot 919), and was used as supplied. Alpha-lactose monohydrate Ph. Eur. was from Merck (lot 2444543). Avicel PH-101 (FMC Corp.) was supplied by C. Barcia, S.A. (lot 5648). Magnesium stearate B.P. was likewise supplied by C. Barcia, S.A. (lot 548). Acetaminophen (lot 841) and furosemide (lot 97) were supplied by UTEFSA. The cellulose-lactose excipients were prepared by us by dry granulation (excipient B) and extrusion-spheronization (excipient C).
1)Characterization of the Drugs Particle Size: Particle size distribution was evaluated in triplicate in a Coulter LS100 laser diffraction apparatus, using water as dispersal medium. For both drugs, mean diameter and standard deviation were estimated after fitting a log-normal distribution.Flow Properties: Bulk density was determined over 20 min in a Hosokawa PT-E Powder Tester operating at 50 taps/min. Compressibility was calculated from the initial and final bulk densities.
6)Compression Properties: 99.5 : 0.5 (w/w) mixtures of drug and magnesium stearate were prepared over 5 min in a Turbula T2C mixer operating at 30 rpm, and samples were tabletted in a Bonals B/MT eccentric apparatus equipped with 9-mm flat punches and a compression data acquisition system.7) Mean yield pressures (Py) were estimated from Heckel plots of the upper punch force-displacement data for three punch cycles.
8)Preparation of Drug-Excipient Mixtures Mixtures (Turbula T2C, 30 rpm, 15 min) of each excipient with each drug were prepared with 12.5 and 37.5% w/w acetaminophen or furosemide.Characterization of the Drug-Excipient Mixtures Flow properties and compression properties of mixtures were characterized by the same methods as for drugs.Tablet Preparation Using the same mixtures and tabletting machine as described above, and a punch pressure of 160 MPa, 250-mg tablets were prepared at 8 tablets/min.Characterization of Tablets Tensile Strength: The crushing strengths of six...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.