PubMed · 11200682
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J Hoffman. 2001. Truth and consequences.. https://doi.org/10.1016/s0161-6420(00)00575-3
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The objective of this study was to prepare and evaluate carrageenan beads as a controlled release system for a freely water soluble drug verapamil hydrochloride and a slightly water soluble drug ibuprofen. Beads were prepared by ionotropic gelation method. The influence of formulation factors (drug content, polymer concentration, counterion type and concentration, outer phase volume) on the particle size, encapsulation efficiency and in vitro release characteristics of beads was investigated. The encapsulation efficiency of veraparnil HCl in the beads (34.8-71.1%) was higher than that of ibuprofen (23.6-58%). While about 30% of ibuprofen was released at 6 h, about 70% of verapamil HCl was released in 5 h from the carrageenan beads prepared.
Synthesis of several polymer-fenoprofen conjugates is described. Fenoprofen was first chemically modified into benzotriazolide 2 and amino acid amide derivatives: glycine fenoprofenamide (3a) and beta-alanine fenoprofenamide (3b) and their benzotriazolides 6a and 6b. Compounds 2 and 6 readily reacted with polyhydroxy aspartamide-type polymers, i.e. poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA) forming conjugates 5, 8a,b and 9a,b, respectively. Conjugate 11 was obtained by partial aminolysis of poly-DL-(2,5-dioxo-1,3-pyrrolidinediyl) (PSI) with 2-aminoethyl fenoprofenamide (3c), followed by total aminolysis with 2-hydroxyethylamine. The synthesised polymer-drug conjugates differed in type of covalent bounding, type and/or length of spacer and drug-loading.
Powder compacts made from acetylsalicylic acid and lactose monohydrate were subjected to an anti-clastic plate bending method in order to obtain the critical stress intensity factor in mode III loading (tearing or antiplane shear mode). The theoretical approach for data processing was based on linear elastic fracture mechanics. In contrast to mode I loading (opening or tensile mode), where above a critical threshold value the critical stress intensity factor is independent of the notch depth, i.e. converts into a true material constant, in mode III loading the critical stress intensity factor could only be presented under strict reference to a defined notch length. For lactose monohydrate, the typical exponential relationship between critical stress intensity factor and plate porosity was found. However, this was not the case for acetylsalicylic acid plates, indicating a change in fracture origin from pores and clusters of pores at higher porosities to machine flaws at low porosities. Hence, no extrapolation to zero porosity was attempted for this material, whereas for lactose monohydrate, the critical stress intensity factor at zero porosity was estimated to be 102+/-14 MNm(3/2). This value is valid for a notch depth of 4.9+/-0.3 mm. From the values obtained for the critical stress intensity factor and the critical strain energy release rate in mode III loading and an anisotropy ratio, here defined as the ratio between the critical stress intensity factors obtained in mode I and mode III loading, it was concluded that acetylsalicylic acid is the more brittle material and that lactose monohydrate behaved rather ductile under the given experimental conditions.