Drug release surface area effect

As an example of a potential limitation, the drugs listed in Figure 1 have rather low molecular weights and relatively similar in molecular size. However, their skin permeation rates vary as much as 100 folds (2 mcg/cm /hr for fentanyl vs. 200 mcg/cm /hr for ephedrine). This difference in skin permeability will be reflected in the size of TDD system required to deliver the effective daily dose (Table I). A TDD system having a drug-releasing surface area of 90 cm is expected to be required for the delivery of diethylcarbamazine at a daily dose of 215 mg/day. From the standpoint of practical applications, a TDD system of this size would not be neither desirable nor economical. 

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. 

FIGURE 11 Effect of surface area on rate of drug release from polymer discs prepared from 3,9-bis(ethylidene-2,4,8,10-tetraoxaspiro-[5,5]undecane) and a 50 50 mole ratio of trans-cyclohexane dimethanol and 1,6-hexanediol at pH 7.4 and 37 C. Polymer contains 4 wt% drug and 0.2 wt% poly(sebasic anhydride). (From Ref. 20.)... 

Improvements in theophylline preparations have come from alterations in the physical state of the drugs rather than from new chemical formulations. For example, the increased surface area of anhydrous theophylline in a microcrystalline form facilitates solubilization for complete and rapid absorption after oral administration. Numerous sustained-release preparations (see Preparations Available) are available and can produce therapeutic blood levels for 12 hours or more. These preparations offer the advantages of less frequent drug administration, less fluctuation of theophylline blood levels, and, in many cases, more effective treatment of nocturnal bronchospasm. 

T. D. Reynolds, S. A. Mitchell, and K. M. Balwinski. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets. Drug Dev. Ind. Pharm. 28 457—466, 2002. 

Equation (6.173) implies that the release rate is governed by the porosity of the membrane, which influences the permeability the polymer material, which influences the semipermeability of the membrane the thickness and surface area of the membrane the solubility and osmotic pressure and the amount of drug in the core. Figure 6.41 shows the effect of osmotic pressure on the release of KC1 from MPOPS. By extrapolating the linear line to zero osmotic pressure, the release rate of drug by diffusion through the microporous membrane structure can be obtained. 

Drugs are applied topically primarily for local effects however, this route can be used to administer drugs for systemic action. Few drugs readily penetrate intact skin. The absorption of drugs that do penetrate the skin is proportional to the surface area over which they are applied and to their lipid solubility. Increased cutaneous blood flow also enhances absorption. Systemic toxicity can become evident when highly lipid-soluble substances (e.g. lipid-soluble insecticides) are absorbed through the skin. Controlled-release patches are now commonly used in human medicine for transcutaneous drug administration. 

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