Class II drug

Digoxin and griseofulvin have about the same solubility ( 20 pg/ml), but a very different dose (0.5 and 500 mg, respectively). Consequently, while digoxin has a very low dose number (0.08), griseofulvin has a dose number, D0, of 133, which indicates that over 331 of water is required to dissolve a single griseofulvin dose. 

GI Physiological Variables Affecting Class II Drug Dissolution 

With very few exceptions, dissolution of the drug substance in the GI tract milieu is a prerequisite for drug absorption following oral administration. For Class II compounds, the rate-limiting factor in their intestinal absorption is dissolution /solubility [23-25]. Hence, in-depth understanding of this process is essential in the oral delivery of low-solubility compounds. Factors governing the dissolution process can be directly identified from the following equation, based on the Nernst-Brunner and Levich modifications of the Noyes-Whitney model [26-28]  

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Class II drugs are classical (3-adrenoceptor antagonists such as propranolol, atenolol, metoprolol or the short-acting substance esmolol. These drugs reduce sinus rate, exert negative inotropic effects and slow atrioventricular conduction. Automaticity, membrane responsiveness and effective refractory period of Purkinje fibres are also reduced. The typical extracardiac side effects are due to (3-adrenoceptor blockade in other organs and include bronchospasm, hypoglycemia, increase in peripheral vascular resistance, depressions, nausea and impotence. 

One example of the application of response surface analysis is a study of critical formulation variables for 20 mg piroxicam capsules [100]. Piroxicam is a BCS Class II drug (low solubility and high permeability). This... 

Crison, G. L. Amidon. pH and surfactant-facilitated in vitro solubilization and dissolution of ketoprofen, a class II drug. Implications for waiver of bioavailability and bioequivalence studies (Unpublished). 

Class II drugs, i.e., low-solubility/high-permeability compounds, are expected to have a dissolution-limited absorption. Thus, for these types of drugs an IVIVC... 

The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

Class II — Drug is poorly soluble, but highly permeable... 

Class II drugs are the p-adrenoceptor antagonists that suppress the sympathetic modulation of the heart action. They are used in the therapy of sinus tachycardia, supraventricular paroxysmal tachycardia and ventricular extra-systoles. Because of its rapid onset and short duration of action, esmolol is the preferred drug in this class for intra-operative use. 

Griseofulvin, a BCS class II drug (Fig. 2), is a well-known example whose poor aqueous solubility causes low and erratic oral bioavailability. As shown below, griseofulvin has a hydrophobic molecular structure, and is practically insoluble in water. Its oral absorption is highly variable, ranging from 25% to 100%, depending on the crystal size. Ultramicrosize griseofulvin preparations were shown to have 100% oral absorption (12). 

Table 3 The Effect of Hydrophilic Excipients on the Dissolution Rates of Griseofulvin (a Biophannaceutical Classification System Class II Drug)...

Nalidixic acid is another example of BCS class II drug, with oral bioavailability limited by poor solubility and slow dissolution (40). Compared to drug powder alone, the solid dispersion of nalidixic acid with P-cyclodextrin or PYP or sodium starch glycolate had much faster dissolution. X-ray diffraction studies revealed the formation of amorphous areas and less degree of crystallinity in the solid dispersion of nalidixic acid with excipients. 

Biopharmaceutical classiLcation depends on both solubility and permeability of one drug. So, insoluble drugs with good permeability are clased as Class II drugs, and insoluble drugs with low... 

Drug A is a large, peptide-like molecule (MW 700 g/mol) and is highly lipophilic and poorly water soluble. It is a BCS Class II drugs. Its oral bioavailability in capsules and conventional tablet formulations is low, yielding practically undetected blood levels. A novel lipid formulation containing a solvent, a high HLB nonionic surfactant, and a fatty acid were developed with sufLcient oral bioavailability for use in the clinic. 

Figure 6.20 Plot of qo vs. 1/0, for the experimental data of Table 6.1 classified in Class II. The curves denote 90% absorption for two particle sizes (from left to right 10 and 25 pm) assigning Pe// = 2 x lCP2cmmin 1, which corresponds [170] to the mean, Papp = 1.68 x 10 5cms 1 of the Caco-2 permeability values of the data [90]. Drugs located above the curves are fully absorbed (Fa > 0.90) Class II drugs. Key (solubility values in) (A) buffer, pH 5.0 (B) fed state simulated intestinal fluid, pH 5.0.

Rinaki, E., Dokoumetzidis, A., Valsami, G., and Macheras, P., Identification of biowaivers among Class II drugs Theoretical justification and practical examples, Pharmaceutical Research, Vol. 21, No. 9, 2004, pp. 1567-1572. 

Class II drugs Dose greater than available binding sites... 

Binding of Class I and Class II drugs to albumin when drugs are administered alone (A,B), or together (C). 

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