Effect of Freezer Programs on Real-Time Storage Results of Dissolution Profiles

Carstensen and Rhodes¹ have suggested that when, in stability programs, assays cannot be performed immediately after the protocol-designated storage time, then freezing them until such a time when assays can be performed would be a reasonable manner to retain the protocol schedule. They caution, however, that such a procedure may not be valid for dissolution data. The article to follow deals with real-time data showing that such a process is feasible for Nalidixic Acid tablets (and presumably for other tablets as well), and that, furthermore, the dissolution pattern would seem to be “frozen” as well.     

Dissolution Profiling of Six Modified-Release Oral Solid Dosage Forms

Dissolution testing was conducted for six non-combination, single entity, modified-release oral solid dosage forms. Dissolution medium was water and 0.1 N hydrochloric acid. USP Apparatus 1 and Apparatus 2 were used arid were rotated at either 50 or 100 rpm. A complete dissolution profile was obtained for all six dosage forms based on their stated dosing interval, D. The three strengths of Theo-dur tablets, Norpace CR 150 mg capsules, and the two strengths of Chlor-trimeton tablets passed the Compendial Case One requirements (USP XXI, 2S, 1906). Thorazine spansules and Quinidex tablets were unable to meet the specifications with water as the dissolution medium; the latter showed improved dissolution character in 0.1 N hydrochloric acid. Tenuate Dospan 75 mg tablets showed good release characteristics in water when the authentic (dosing interval (D = 24 hours) was changed to a modified dosing interval of D* = 12 hours. All dissolution aliquots were assayed by UV absorbance measurements at the absorbance maximum for each drug and were also checked for excipient interference. Newer drugs appearing on the market will be more likely candidates for meeting compendial specifications; modified-release pharmaceuticals that appeared before the new specifications may have to be allocated specifically expanded window percentages.     

The Effect of Organic Ligands on the Rate of Loss of Phenylmercuric Nitrate into Rubber Closures and Plastic Containers

The effect of the presence of various organic compounds containing a variety of functional groups on the rate of loss of phenylmericuric (PM) nitrate into plastic containers and rubber closures has been investigated. The presence of organic compounds profoundly influenced the loss of the phenylmercuric nitrate, that loss being dependent upon their chemical structure and concentration. This effect explains the unpredictability of the loss of PM nitrate into polymer matrices from pharmaceutical products.     

Bonelike apatite formation on carbon microspheres

Carbon microspheres with a diameter of 2 μm were prepared by hydrothermal process. The apatite-formation ability of the carbon microspheres was evaluated by soaking them in a simulated body fluid (SBF) for 5 and 10 d and apatite-formation mechanism was also analyzed. The result showed that bonelike apatite was formed on the surface of carbon microspheres. Our study indicates that the carbon microspheres synthesized by this method possess apatite-formation ability and may be used as a bioactive injectable filler for bone tissue regeneration.     

Frictional assessment of magnesium stearate and palmitate lubricant powders

A method has been developed for the frictional assessment of powder lubricants using a shear-box tester similar to that employed by Jenike. One commercial magnesium stearate, three high-purity magnesium stearates and three high-purity magnesium palmitates were assessed using this method. Powders with a well-ordered crystal structure and particle shape have a lower initial maximum coefficient of friction μ_a. The difference between μ_a and μ_b, the equilibrium dynamic friction coefficient, gives an indication of lubricant film-forming propensity. The basic friction equation is obeyed by the powders for most of the load range studied but deviates slightly approaching zero normal load.     

Response to Zenz and Altiner

Ordered mixes were produced using a fructose-based excipient as a coarse carrier component and fine-particle pyridoxine hydrochloride (vitamin B₆) as the adherent component. Prior to mixing, the fructose agglomerates were conditioned for 48 h at either 0% RH or 55% RH at 20 °C. Under these conditions, one lot of fructose had a moisture content of 0.24 wt.% and the other lot had a moisture content of 0.74 wt.%. Following mixing, the powders were subjected to vibration at various frequencies in the range 25 to 200 Hz and accelerations in the range 9.81 to 39.24 m/s². It was found that whilst ordered mixes produced using fructose at 0.24 wt.% moisture content were unstable, those produced using 0.74 wt.% moisture content fructose were extremely stable and segregation resistant.The formation of ordered units with increased adhesion in carriers with higher moisture content suggested that these ordered mixes could be considered as spontaneous granulations.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.