Abstract:
:The objective of this study was to determine the primary formulation properties that affect the dissolution rate of poorly soluble nondisintegrating drugs. This work focused on compression of orally administered acidic drugs with ionizable buffers. Naproxen was used as the poorly soluble model drug, and calcium salts of carbonic, citric, and phosphoric acids were used as formulation buffers. Gastrointestinal tract (GI) dissolution was simulated in a laminar flow apparatus by exposing a drug/buffer tablet to aqueous solution of a given pH at a constant flow rate. Although formulation with a buffer resulted in reduced available drug surface area, the absolute drug dissolution rate and flux increased with increased buffer content to a maximum from tablets having equal weights of drug and buffer. This buffer-induced enhancement was seen not only in GI tract simulation (pH 7), but also at pH 2 (stomach conditions), where acidic drugs remain in their poorly soluble form upon dissolution. The flux increase was much greater than that achieved by using the same amount of an inert excipient in the solid formulation. Dissolution rates were also increased by decreased drug and buffer particle sizes and increased fluid flow rate. Drug dissolution rates were inversely proportional to intrinsic buffer solubilities: The model drug actually dissolved fastest when the buffer solubility was lower than that of the drug. Dissolution rates were apparently insensitive to the relative proximity of the drug and buffer ionization constants.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Chakrabarti S,Southard MZdoi
10.1021/js960334fsubject
Has Abstractpub_date
1997-04-01 00:00:00pages
465-9issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(15)50284-0journal_volume
86pub_type
杂志文章abstract::p-Bromospiperone was prepared from the reaction of spiperone with bromine. It was tested for dopamine receptor binding affinity in vitro and its ability to stimulate prolactin secretion in vivo. The results indicate no significant change of biological activities due to the bromination of spiperone. ...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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abstract::Hyperthermia (HT)-dependent cisplatin (CDDP) release and tumor CDDP level increase after the administration of thermosensitive, large unilamellar vesicles (LUVs: LUV-1 and LUV-2) and a thermosensitive, small unilamellar vesicle (SUV: SUV-1) were examined in comparison with those following administration of a non-therm...
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abstract::The promoting efficacies of N-acyl derivatives of amino acids on the rectal absorption of sodium ampicillin were investigated using the rat rectal loop technique. N-Acyl derivatives with longer carbon chains in the acyl moiety showed a greater promoting potency. The promoting potencies of N-acyl derivatives of phenylg...
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journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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