Drug release surface area

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. 

The rate and duration of steroid release is affected by (1) polymer composition, (2) drug/polymer ratio (3) microsphere size distribution, and (4) microsphere quality (75). The ratio of glycolide to lactide in the copolymer has been found to be more dominant than the polymer molecular weight in the design of controlled release formulations. Microspheres of smaller size provide in vivo drug profiles of higher levels and shorter durations because of greater surface area. 

Surface erosion not only leads to zero-order drug release from devices that maintain a constant surface area, but has other important consequences. Among these are the following (1) the rate of drug release is directly proportional to drug loading, (2) the lifetime... 

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.)... 

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. 

Methods for synthesizing highly porous microspheres were investigated, and surface area measurements were used to confirm the porous nature of the samples [19]. A high surface area was measured and was compared with the calculated surface area value. The measured value was 35 times that of a nonporous particle, indicating the extensive porosity of the spheres. The surface area was also used to explain the drug release mechanisms in the pores of these systems. 

The Sartorius Absorption Model (26), which served as the forerunner to the BCS, simulates concomitant release from the dosage form in the GI tract and absorption of the drug through the lipid barrier. The most important features of Sartorius Absorption Model are the two reservoirs for holding different media at 37°C, a diffusion cell with an artificial lipid barrier of known surface area, and a connecting peristaltic pump which aids the transport of the solution or the media from the reservoir to the compartment of the diffusion cell. The set-up is shown in Figures 7a and b. 

The gas rises into the transverse colon and can form temporary pockets, which can restrict access of water to the formulation, particularly if the design does not permit uptake of water through the surface. For this reason, distal release of drug can be hampered by poor wetting/spreading and the reduced surface area, leading to restricted absorption. 

P a Membrane surface area Drug release mechanisms... 

The self-emulsifying behaviour of a binary nonlonlc surfactant vegetable oil mixture has been shown to be dependant on both temperature and surfactant concentration. The quality of the resulting emulsions as assessed by particle size analysis showed that manipulation of these parameters can result In emulsion formulations of controlled droplet size and hence surface area. Such considerations are Important when the partition of lipophilic drugs Into aqueous phases and drug release rates are considered. 

Studies using smaller implants of 2.9 mm diameter indicated statistically significant differences in the two rate constants (Table 2) and extent of drug released from the implant in comparison with implants of mean diameter 6.2 mm. This could be attributed to an increase in surface area per unit volume of the smaller implant. 

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. 

The transdermal system provides continuous systemic delivery of fentanyl for 72 h. The amount of drug released from the system per hour is proportional to the surface area. Following application of the patch to the skin, a depot of fentanyl concentrates in the upper skin layers. This is then available to the systemic circulation. There is an initial rise in blood fentanyl concentration after application followed by a leveling off that occurs 12 to 24 h later. Peak blood concentrations occur between 24 and 72 h after application. The skin does not appear to metabolize fentanyl when delivered transdermally. 

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