Zero-order drug release profiles

Irrespective of administration route, sustained-release profiles or even zero-order drug release profiles are often required of the active pharmaceutical ingredients, in order to maintain relatively consistent plasma concentrations. Biotextiles as DDSs achieve the required sustained-release characteristics mainly by virtue of the physico-chemical properties of polymers when the active ingredients are dissolved or dispersed within the matrices. This can also be accomplished because of their particular structure, for example when the fibers are employed as drug reservoirs in the core/shell. Most of the biotextiles mentioned are designed to achieve sustained drug delivery. 

Fig. 1 Drug level versus time profile showing differences between zero-order controlled release, slow first-order sustained release, and release from a conventional tablet or capsule.

The property that makes polyanhydrides unique is their surface hydrophobic-ity. Due to this high hydrophobicity, polyanhydride matrices do not facilitate water absorption. Consequently, hydrolytic degradation is restricted to the surface—a property that is termed as surface erosion. This type of degradation allows for zero-order release of drugs, i.e., the drug release profile is independent of the residual concentration of the drug in the matrix. 

Fig. 17 Syncro-Mate-C implant, a subdermal implant fabricated from the microreservoir dissolution-controlled drug-delivery system, and subcutaneous controlled release of nor-gestomet, a potent synthetic progestin, at constant rate for 20 days. The open ends on the implant do not affect the zero-order in vivo drug release profile. (Adapted from Ref. . )...

M. Donbrow, Y. Samuelov, Zero order drug delivery from double-layered porous films release rate profiles from ethylcellulose, hydroxypropylcellulose and polyethylene glycol mixtures, / Pharm Pharmacol, 32 463-470,1980. 

The release curve of ketoprofen obtained from the KET-R tablet at pH 1.2 and 50 rev/min is shown in Fig. 1. The release profile was zero order up to 90% drug content. The equation obtained by plotting the percentage released vs. time was y=0.187x-1.997, 0.99. No burst effect was present. 

The release profile of ketoprofen from the 2/3 CAP coated core (KET-R CAP tablet) was of zero order (y=0.037x-1.263, r=0.99) and the drug release rate was clearly lower than the original core, as is shown in Fig. 5. However, the technique of preparation of KET-R CAP tablets was somewhat complex, requiring considerable accuracy in the partial coating phase, and not easily applicable on an industrial scale. 

If tlie release characteristics of the formulation can be described by a zero-order process for some period of time (e.g., 5%/hr from 4 to 12 hours), and the dissolution profile appears to fit a linear function for that period of time, a release rate specification may be established to describe the dissolution characteristics of that formulation. A release rate specification may be an addition to the specifications established on the cumulative amount dissolved at the selected time points. Alternatively, a release the rate specification may be the only specification except for the specification for time when at least 80% of drug has dissolved. 

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