Drugs, dissolution

The rate at which a solid substance dissolves in its own solution is proportional to the difference between the concentration of that solution and the concentration of the saturated solution. 

Early studies in this field of research formulated two main models for the interpretation of the dissolution mechanism the diffusion layer model and the 

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FIGURE 14 In vitro rate of release of testosterone from a PCL capsule (reservoir device), illustrating rate control by drug dissolution when the polymer membrane thickness is small. (From Ref. 68.)... 

Peh KK, Lim CP, Qwek SS, Khoti KH. Use of artificial networks to predict drug dissolution profiles and evaluation of network performance using similarity profile. Pharm Res 2000 17 1386-98. 

Diarrheal conditions may decrease drug absorption as a result of reduced intestinal residence time. The absorption of several drugs was decreased in response to lactose- and saline-induced diarrhea [145]. Digoxin absorption from tablets was impaired in one subject who developed chronic diarrhea as a result of x-ray treatment [146]. Abdominal radiation or the underlying disease has been shown to reduce digoxin and clorazepate absorption [147]. A dosage form that provides rapid drug dissolution (e.g., solution) may partially resolve this problem. 

Fig. 21 Effect of croscarmellose sodium (type A) on drug dissolution from hard gelatin capsules (filler, dicalcium phosphate lubricant, 1% magnesium stearate). (From Ref. 132.)...

KB Shah, LL Augsburger, K Marshall. Multiple tamping effects on drug dissolution from capsules filled on a dosing-disk type automatic capsule filling machine. J Pharm Sci 76 639-645, 1987. 

AM Mehta, LL Augsburger. A preliminary study of the effect of slug hardness on drug dissolution from hard gelatin capsules filled on an automatic capsule filling machine. Int J Pharm 7 327-334, 1981. 

FS Horn, JJ Miskel. Enhanced drug dissolution rates for a series of drugs as a function of dosage form design. Lex Sci 8(1) 18-26, 1971. 

The intrinsic dissolution rate is usually evaluated by using a rotated disk method (Fig. 7). The pure powdered solute is compressed in a die under high pressure, in the absence of any excipients. The resulting nondisintegrating disk is then transferred to a dissolution cell which has sufficient volume to maintain sink conditions. The die is rotated at a certain speed, and the rate of drug dissolution is then measured. 

A Shah, K Nelson. Evaluation of a convective diffusion drug dissolution rate model. J Pharm Sci 64 1518, 1975. 

S Chakrabarti, MZ Southard. Control of poorly soluble drug dissolution in conditions simulating the gastrointestinal tract flow. 1. Effect of tablet geometry in buffered medium. J Pharm Sci 85 313-319, 1996. 

M Westerberg, C Nystrom. Physicochemical aspects of drug release. XVII. The effect of drug surface area coverage to carrier materials on drug dissolution from ordered mixtures. Int J Pharm 90 1-17, 1993. 

C Doherty, P York. Microenvironmental pH control of drug dissolution. Int J Pharm 50 223-232, 1989. 

JR Crison, VP Shah, JP Skelly, GL Amidon. Drug dissolution into micellar solutions Development of a convective diffusion model and comparison to the film equilibrium model with application to surfactant-facilitated dissolution of carbama-zepine. J Pharm Sci 85 1005-1011, 1996. 

JR Crison, GL Amidon. The effect of particle size distribution on drug dissolution A mathematical model for predicting dissolution and absorption of suspensions in the small intestine. Pharm Res 10 S170, 1992. 

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