Drug delivery monolithic device

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

Adhesive patches may also be monolithic or multilayered devices of the reservoir or matrix type for either systemic or local drug delivery (Fig. 8). The two main manufacturing processes to prepare adhesive patches are solvent casting and direct milling (with or without a solvent). The intermediate product is a sheet from which... 

The buccal permeability of the non-steroidal antiinflammatory drug, diclofenac sodium, has been evaluated in a dog model. The dog was selected because of the similarity of its buccal mucosa to that of man. Analysis of the buccal data indicated that diclofenac sodium permeability followed an essentially zero-order kinetic process with a minimal lag phase. Permeability of the drug was estimated to be 3 mg/cm2.h but significant differences were observed between animals. The absorption rate with the transbuccal delivery device decreased with time whereas the corresponding rate with a saturated solution was constant. This difference was attributed to the time dependency of drug delivery from the device and was modeled on the basis of release from a membrane-dispersed monolith combined with constant buccal permeability. The predictions of the model showed excellent agreement with the experimental data. 

In developing such devices, two fundamentally different approaches are possible. In one, mechanism of drug release is by diffusion from a reservoir through a rate-limiting bioerodible pol3nner membrane, and in the other, drug release is controlled by matrix erosion. However, to achieve zero order drug delivery from monolithic erosional devices the erosion process must be confined to the surface of the solid device. ... 

The polymer will play a passive role if it acts solely as a barrier which controls the rate of drug delivery by diffusion. Indeed, changes in the properties of the polymer are undesirable in this case since thereby the parameters governing the diffusion process will change. Purely diffusion controlled delivery systems generally belong to either one of two types, monolithic devices or reservoir devices. 

The authors manufactured a monolithic device made of a NIPAAm-BMA copolymer gel with a film thickness of 0.5 mm and a diameter of 15 mm in which the nonsteroidal drug, indomethacin, was used as the model drug. The drug delivery behavior of this system was measured. After the initial delivery, 0th delivery was observed (Fig. 7(a)). The delivery rate accel-... 

Diffusion-controlled membranes exist in two categories depot systems, in which the drug is totally encapsulated within a reservoir, and monolithic systems, where the drug is dispersed in a rate-controlling polymer matrix [25]. One commercially successful depot device is the Alza Ocusert for ocular delivery of pilocarpine in the treatment of glaucoma [25]. 

The cumulative release profile for diclofenac sodium from the transbuccal delivery device exhibited a square root of time dependency over approximately 80% of the total release process (Figure 3). In view of the drug s solubility within the hydrogel ( 16 mg/cc) and the total loading (-420 mg/cc), dyjg2release was modelled as a dispersed monolith and a 3.19 x 10 cm /h diffusion coefficient was calculated. 

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