Aspirin slow release

Slow-release versions of aspirin for long-term use as an anti-inflammatory drug are described in U.S. 5,855,915. Estimate the cost of production of each of the slow-release formulations given. 

The absorption of normal doses of regular aspirin from the GI tract is generally rapid, with peak serum concentration achieved within 2 hours. This peak value may be delayed for 12 hours or longer for enteric-coated or slow-release formulations. Moreover, toxic doses of aspirin may form concretions or bezoars and produce pylorospasm, thereby delaying absorption. Serum salicylate in such instances may not reach maximum concentration for 6 hours or longer, an important consideration when the assessment of the severity of toxicity is based on such measurements. 

Aspirin absorption may be delayed when overdose quantities are consumed, especially of enteric-coated or slow-release preparations. This must be considered when interpreting serum salicylate values, especially for specimens obtained earlier than 6 hours after ingestion. Repeat testing within 2 to 3 hours is recommended to ensure that absorption is complete subsequent testing provides an indication of effectiveness of therapeutic intervention. Because of the aforementioned complications, proper assessment of salicylate intoxication requires sound clinical evaluation in combination with serum salicylate levels. 

A random cross section of the voluminous literature on microencapsulation of drugs within PLA (or, more often, PLA/PGA copolymers— but for this chapter the distinction will not be made as the HSP of PGA are not far from PLA) shows the need for some unifying principles. The first key question is whether the drug is sufficiently insoluble in the PLA that it is present only inside the capsule. Even crude HSP calculations can give some idea of this. In our simple example, one would expect a Hckian diffusion, linear with respect to the square root of time, for aspirin dissolved in the PLA. This is the classic behavior of a diffuser that is soluble in the matrix. The ibuprofen would be expected to show zeroth-order slow release by diffusion through the membrane from the pool in the center, classic behavior for systems where the mutual solubility is poor. 

Gastric mucosal injury and occult blood loss can be reduced, but not prevented by the use of buffered effervescent, slow-release and enteric coated preparations of aspirin (79>, 82, 83=, 88=, 117=-119=, 120, 121). The presence of particulate aspirin is thought to be important, but aspirin and salicylic acid given in solution produced multiple lesions in rats (122). Even parenteral aspirin produces and enhances gastric mucosal lesions and bleeding (123). Carben-oxolone does not prevent the fall in gastric mucosal potential difference produced by aspirin in man (110=). 

Microencapsulation is a common means of providing sustained release of a medication and is frequently used in the pharmaceutical industry for this purpose. For example, aspirin which provides effective relief for fever, inflammation, and arthritis, can cause peptic ulcers and bleeding in direct doses. Therefore, it is sometimes encapsulated in ethyl cellulose or hydroxypropyl methylcellulose and starch tablets are produced by pressing together these microcapsules. Instead of being released all at once, the encapsulated aspirin diffuses through the shell producing a slow and sustained release. 

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