Evolution of a physiological pH 6.8 bicarbonate buffer system: application to the dissolution testing of enteric coated products.

The use of compendial pH 6.8 phosphate buffer to assess dissolution of enteric coated products gives rise to poor in vitro-in vivo correlations because of the inadequacy of the buffer to resemble small intestinal fluids. A more representative and physiological medium, pH 6.8 bicarbonate buffer, was developed to evaluate the dissolution behaviour of enteric coatings. The bicarbonate system was evolved from pH7.4 Hanks balanced salt solution to produce a pH 6.8 bicarbonate buffer (modified Hanks buffer, mHanks), which resembles the ionic composition and buffer capacity of intestinal milieu. Prednisolone tablets were coated with a range of enteric polymers: hypromellose phthalate (HP-50 and HP-55), cellulose acetate phthalate (CAP), hypromellose acetate succinate (HPMCAS-LF and HPMCAS-MF), methacrylic acid copolymers (EUDRAGIT® L100-55, EUDRAGIT® L30D-55 and EUDRAGIT® L100) and polyvinyl acetate phthalate (PVAP). Dissolution of coated tablets was carried out using USP-II apparatus in 0.1M HCl for 2h followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, the various enteric polymer coated products displayed rapid and comparable dissolution profiles. In pH 6.8 mHanks buffer, drug release was delayed and marked differences were observed between the various coated tablets, which is comparable to the delayed disintegration times reported in the literature for enteric coated products in the human small intestine. In summary, the use of pH 6.8 physiological bicarbonate buffer (mHanks) provides more realistic and discriminative in vitro release assessment of enteric coated formulations compared to compendial phosphate buffer

Facilitated diffusion in the dissolution of carboxylic polymers

Carrier-mediated transport plays an important role in the dissolution of carboxylic polymers in aqueous solutions. Experiments with a rotating disk apparatus showed that the rate of polymer dissolution increased significantly with the addition of proton-carriers over the pH range of 6 to 13. The facilitated diffusion phenomenon in the dissolution of carboxylic polymers differs from that in membrane and biological systems in that the transport of polymer chains is not directly facilitated by any carriers. Proton-carriers facilitate the diffusion of hydrogen ions away from the polymer interface. As the concentration of hydrogen ions at the polymer interface decreases, the polymer solubility at the interface increases significantly, leading to a substantial increase in the polymer concentration driving force and, hence, the diffusion rate. A homogeneous chemico-diffusion model that elucidates the effects of the solution pH, the concentration and acidity of carriers, and the polymer acidity on the facilitated diffusion was developed. Good agreement between experimental and theoretical results was achieved. There are optimum values of the carrier's pK a , and of the solution pH which give a maximum facilitation effect. As the diffusion rate of the polymer is increased by the carrier, the overall polymer dissolution process changes from diffusion-limited to disentanglement-limited. © 2005 American Institute of Chemical Engineers AIChE J, 51: 415–425, 2005Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34253/1/10329_ftp.pd

Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

BACKGROUND: Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP), a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. METHODS: The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. RESULTS: The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP (in soluble form) and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold) diminished in the presence of SP (33.3%). Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. CONCLUSION: The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP) or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors

The effects of physical variables on zooplankton distributions in stratified lakes.

University of Minnesota Ph.D. dissertation. October 2007. Major: Civil Engineering. Advisor: Miki Hondzo. 1 computer file (PDF); xi, 136 pages. Ill. (some col.)Zooplankton play a vital role in lake ecosystems. They serve as an important food source for fish, as well as being major consumers of algae, which contributes to greater water clarity. To understand the dynamics in a lake, it is necessary to understand zooplankton and how they are affected by the physical environment around them. The purpose of this research was to address the question of how turbulence and temperature stratification affect zooplankton aggregations in lakes. Laboratory experiments were performed to quantify the effects of temperature and turbulence on zooplankton distributions in a stratified tank. These measurements were designed to measure zooplankton aggregations and to provide detailed information on the physical conditions causing them. Comprehensive field measurements were taken throughout one summer, covering five 24-hour periods, in order to investigate the effects of temperature and turbulence on zooplankton aggregations in the field. A high-frequency sonar measurement device was developed to take the measurements by modifying the output of a commercial fish-finder and calibrating it to match zooplankton net counts. Our results showed that zooplankton distributions are strongly affected by temperature and turbulence, and that these effects are species-specific, and are different between day and night