Understandingabsorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.

Similarity and Difference in Distribution of Estrogen Receptor-alpha Protein in Artificially Differentiated and Senescent Neuronal Cultured Cell

BACKGROUND: We tried to see if the change in subcellular distribution of estrogen receptor alpha(ER-alpha) was occurring in the senescent or differentiated cells. And if any, we also tried to observe the similarities or differences of distribution changes in ER-alpha in these two groups. METHODS: By treatment with 3'-Azido-3'-deoxythymidine(AZT, Sigma-Aldrich, USA, 1micrometer) on PC12 pheochromocytoma cells line(ATCC CRL-1721). Immunohistochemistries with anti-ER-alpha antibody were also performed on the cells without treatment of AZT, with treatment of 74 days and 140 days. The same staining was also done on the arti-ficially differentiated cells induced by nerve growth factor(50ng/ml) for 5 days. The distribution of ER-alpha in these two cell groups were compared by confocal laser microscope. RESULTS: Senescent PC12 cells treated with AZT showed the changes in morphologies or cell sizes, comparing with normal counterparts. Subcellular localization of ER-alpha in cytoplasmic compartment increased in the cells treated with AZT during much longer duration. Same change in subcelluar distribution was also identified in the cells treated with NGF. In fully differentiated cells, we could find the presence of ER-alpha mainly in the cytoplasmic compartment. However, as to the organelles expressing ER-alpha, senescent and differentiated cells showed differences; mainly expressed in mitochondria in differentiated cells; but expressed diffused in cytoplasm in senescent cells. CONCLUSION: We could see the similarities in subcellular distribution of ER-alpha in the artificially senescent and differentiated neuronal cells. Increase in cytoplasmic expression of ER-alpha in cytoplasm was found in much senescent or differentiated cells. Considering that cell proliferation decrease both in senescence and differentiation, increase in ER-alpha in cytoplasmic compartment might be caused by decrease in cell proliferation of these two changes. This means that estrogen might play a role in inhibiting cell proliferation via its increased receptors within cytoplasmic compartment. In addition, we also found the differences in organelles expressing ER-alpha in both cases, suggesting that minor differences in mechanism for action of estrogen in both cases of senescent and differentiated cells. Estrogen might play a major role through mitochondria in cell differentiation; but not in cell senescence.

Conformation of azidothymidine: an anti-AIDS drug.

The nucleoside antibiotic, 3'-azido-3'-deoxythymidine, or simply, azidothymidine has shown great promise in inhibiting the human immuno deficiency virus and in reducing mortality among AIDS patients. Conformational properties of azidothymidine have been investigated by quantum-mechanical PCILO method and compared with those of the parent nucleoside, thymidine. The results indicate great similarity between them and this similarity is remarkably striking in the situations that prevail in aqueous solution. This result has important biological significance in explaining the drug action of azidothymidine.

Study of pharmacokinetics of AZT in mice by encapsulation in liposomes Containing galactosylceramide / 中国药理学通报

AIM To study the pharmacokinetics of AZT in mice by encapsulation in liposomes Containing galactosylceramide (GalCer). METHODS AZT was encapsulated in liposomes containing GalCer and the pharmacokinetics of AZT-GalCer and free AZT were observed in mice. RESULTS Higher concentration of AZT in mice injected AZT-GalCer was found in plasma after 30 min and it was ten times as high as in mice injected with AZT. On the other hand, Ke decreased significantly from 0.037 to 0.021 h -1 , T_ 1/2 Ke increased significantly from 19 min to 35 min, and AUC was 2.77 times as high as in mice injected with AZT. CONCLUSIONS AZT-GalCer serving as a dilivery carrier could prolong the effective concentration of AZT in plasma. AZT-GalCer might have great therapeutic potential for treating AIDS.-