Drug dissolution time

While solution crystallization is the main focus of this book, there are applications which are special cases of the CrystaUization methods described in earher chapters. For example, a process requiring sterile crystallization is a special example of an antisolvent addition and is presented in Example 11-1. In this particular example, it is necessary to produce fine particles in order to meet drug dissolution time specifications in the final single-dose vials. Furthermore, the material is thermally unstable. Therefore, special precautions have to be taken to minimize any degradation during processing. 

An alternative approach was reported (49) in which tobramycin was directly incorporated into a porcine scleral shield with a 72-hr dissolution time by immersion in a solution of the drug. After implantation in rabbit eyes for up to 8 hr, the shields were removed and the concentration of antibiotic in the corneas and aqueous humor... 

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. 

S. Yamamura, F. Aida, Y. Momose, and E. Fukuoka, Analysis of mean disintegration time and mean dissolution time by moment analysis microcalorimetric curves, Drug Dev. Ind. Pharm., 26, 1 (2000). 

Heterogeneous conditions both in terms of hydrodynamics and composition prevails in the GI tract. Parameters such as D, Cs, V, and h are influenced by the conditions in the GI tract which change with time. Thus, time dependent rate coefficients govern the dissolution process under in vivo conditions. One of the major sources of variability for poorly soluble drugs can be associated with the time dependent character of the rate coefficient, which governs drug dissolution under in vivo conditions. 

Drug dissolution is the dynamic process by which solid material is dissolved in a solvent and characterized by a rate (amount/time), whereas solubility describes an equilibrium state, where the maximal amount of drug per volume unit is dissolved. The solubility, as well as the dissolution, in a water solution depends on factors such as pH, content of salts and surfactants. 

The absorption of class III drugs is limited by their permeability over the intestinal wall. Thus, as this process is not at all modeled by the classical in vitro dissolution test, no IVIVC should be expected. When drug dissolution becomes slower than gastric emptying, a reduction in the extent of bioavailability will be found in slower dissolution rates as the time when the drug is available for permeation over the gut wall in the small intestine will then be reduced. Thus, the same type of relationship can be expected between bioavailability and in vitro dissolution, as shown in Fig. 21.12 for a class I drug. 

In pharmaceuticals, NIR is used for, of course, moisture, polymorphic (drug) forms, percent crystallinity, isomer purity, tablet/capsule assay, coating levels, evaluation of dissolution times, and numerous process tests. It is a rapid means for the Food and Drug Administration to check for counterfeit drugs, and for the Drug Enforcement Agency to ascertain what type of materials are impounded in drug raids. ... 

Three correlation levels have been defined and categorized in descending order of the ability of the correlation to reflect the entire plasma drug concentration-time curve that will result from administration of a dosage form. The relationship of the entire in vitro dissolution curve to the entire plasma level curve defines the correlation. 

Refinement and expansion of these steady-state mass balance approaches has led to the development of dynamic models which allow for estimation of the fraction absorbed as a function of time and can therefore be used to predict the rate of dmg absorption [37], These compartmental absorption and transit models (CAT) models have subsequently been used to predict pharmacokinetic profiles of drugs on the basis of in vitro dissolution and permeability characteristics and drug transit times in the intestine [38],... 

The lag time evident in the dissolution profile of the second dose is determined by the progressive gelation of the intermediate barrier in addition, since the dissolution medium permeates the barrier very slowly and wets the third layer, the disintegrant efficiency could be reduced, thus resulting in a significant decrease of drug dissolution rate. 

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