Dissolution administered drugs

Absorption of orally administered drugs depends mainly on dissolution if the compound is poorly soluble but highly... 

Orally Administered Drug Products Dissolution Data Analysis with a View to In Vitro-ln Vivo Correlation... 

In order to obtain a clinical effect by an orally administered drug, it is, for example, required that the drug is (i) dissolved and released from its formulation, (ii) transported over the mucosal barrier, and (iii) has passed from the lumen to the systemic blood circulation without being metabolized by, for example, the lumen or the liver. The drug dissolution rate and the rate of absorption of the dissolved active substance as well as the relation between these processes are important, in particular the dissolution process since the absorption of undissolved drug particles can be disregarded. 

Absorption of many orally administered drugs is controlled by dissolution rate. Amorphous forms generally dissolve faster than crystalline forms because no energy is needed to break up the crystal lattice. 

The amount of liquid in the rectum has been reported to be about 3 ml. This is small compared to the volume of fluid available throughout the GI tract when a drug is administered orally. Such a small volume of fluid can limit dissolution of drugs, particularly those with low aqueous solubility. It also may be a constraint to the rapid dissolution and release of compounds from water-soluble vehicles where dissolution of the vehicle is considered to be the rate-determining step in drug release from the vehicle. 

Presentation in powder form permits drugs to be reduced to a very fine state of division, which often enhances their therapeutic activity or their efficacy by an increase of dissolution rate and/or absorption.f Divided powders are also found to be convenient for administering drugs that are excessively bitter, nauseous, or otherwise offensive to the taste. 

The pH varies in the GI tract from 1 to 8 (see Table 4.5), and so the dissolution properties should therefore be known over this pH range for orally administered drugs. A more thorough review of intestinal pH conditions can be found elsewhere (Charman et al. 1997). 

The time to reach the effective blood level of the orally administered drug is too long because of the low dissolution rate, even in case of a complete absorption. There is no aqueous eye drop or injectable solution or other liquid formulation that can be prepared because of the low solubility. 

For an orally administered drug to have a therapeutic effect, the drug molecules must be dissolved in the gastrointestinal (GI) fluids, pass through GI membrane to the circulatory system, and reach the target in sufficient quantity. That is, drug molecules must be dissolved in aqueous-based GI fluids in sufficient quantity to have any therapeutic effect. If the solubility of the drug in GI fluids is not sufficient, the bioavailability will be compromised as the absorption will be solubility limited. It is quite common for poorly soluble compounds to also dissolve slowly. If the dissolution... 

Fig. 6 This schematic is an illustration of the GIT advanced compartmental transit model (stomach, seven small intestine compartments, colon, and nine enterocytes). The administered drug, after dissolution, becomes available for passive absorption and efflux secretion. The rate of drug transfer into and out of enterocyte compartments for each GIT lumen compartment is calculated by using the concentration gradient across the apical and basolatmal membranes. This figure is published with permission (Agoram et al. 2001)...

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