Kinetics release

An important question arising from the aerogel modification is how are the release kinetics of the drug influenced by the functional groups The release kinetics depend on 

These findings allow the release rate to be adjusted to some extent according to the desired application. Hydrophilic aerogels used as a carrier material accelerate the dissolution of poorly soluble drugs and thus improve their bioavailability. Hydrophobic aerogels slow down the dissolution rate and thus can be used for ItMig-term drug release systems. 

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Release kinetics of the matrix system have been derived (80) and refined (81) ... 

The optimum conditions for polyion complex formation between chitosan and hyaluronate were identified fhe compression exerfed fo manufacture the implant had no role to play in the release kinetics [28,92]. Various authors published data confirming fhaf fhe combinafion of chifosan and hyaluronic acid is always suscepfible fo swelling, even in fhe presence of cross-hnking. 

Recently, Brich and coworkers (40) reported the synthesis of lactide/glycolide polymers branched with different polyols. Polyvinyl-alcohol and dextran acetate were used to afford polymers exhibiting degradation profiles significantly different from that of linear poly-lactides. The biphasic release profile often observed with the linear polyesters was smoothened somewhat to a monophasic profile. Further, the overall degradation rate is accelerated. It was speculated that these polymers can potentially afford more uniform drug release kinetics. This potential has not yet been fully demonstrated. 

Because of the extreme differences between conventional pharmaceuticals and the protein molecules in terms of formulation techniques and drug release kinetics, the two categories will be discussed separately here. 

Recently, Tsakala et al. (90) formulated pyrimethamine systems based on several lactide/glycolide polymers. These studies were conducted with both microspheres (solvent evaporation process) and implants (melt extrusion process). In vitro studies indicated that pyrimethamine-loaded implants exhibited apparent zero-order release kinetics in aqueous buffer whereas the microspheres showed an initial high burst and considerably more rapid drug release. In vivo studies in berghi infected mice confirmed that the microspheres did not have adequate duration of release for practical application. However, the implants offer promise for future clinical work as more than 3 months protection was observed in animals. 

Extensive studies have been reported with cisplatin in the field of chemoembolization (59,98). Microspheres prepared by a solvent evaporation procedure were characterized in vitro and critical processing parameters in regard to drug release kinetics were identified. 

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. 

The incorporation and release kinetics from polyanhydride matrices of a number of drugs have been studied. Representative examples of several of these are described below. 

These two methods produce different release profiles in vitro. Figure 5 demonstrates the release kinetics of BCNU from wafers loaded with 2.5% BCNU pressed from materials produced using these two methods. The wafers containing tritiated BCNU were placed into beakers containing 200-ml aliquots of 0.1 M phosphate buffer, pH 7.4, which were placed in a shaking water bath maintained at 37 C. The shaking rate was 20 cycles/min to avoid mechanical disruption of the wafers. The supernatant fluid was sampled periodically, and the BCNU released was determined by liquid scintillation spectrometry. The BCNU was completely released from the wafers prepared by the trituration method within the first 72 hr, whereas it took just about twice as long for the BCNU to be released from wafers... 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

N Ammoury, H Fessi, JP Devissaguet, F Puisieux, S Benita. In vitro release kinetic pattern of indomethacin from poly (d,l-lactide) nanocapsules. J Pharm Sci 79(9) 763-767, 1990. 

A challenge in designing liposome systems is the assessment of drug release from such systems in vitro. Use of agarose gel matrices has been reported as one approach to evaluate the release kinetics of liposome-encapsulated materials in the presence of biological components [68],... 

A device designed to determine the transport of an epidermal growth factor from a Pluronic gel, a Carbopol gel, and a vanishing cream base was shown capable of demonstrating formulation-dependent release kinetics [22], This device consists of a release cell which has a membrane to minimize release due to mechanical breakdown and is placed in a stirred and temperature-controlled receptor fluid. 

Benita, S. and Donbrow, M. (1982) Dissolution rate control of the release kinetics of water-soluble compounds from ethylcellulose film-type microcapsules. International Journal of Pharmaceutics, 12, 251-264. 

The Johnson dissolution models described above postulate that h varies linearly with partide size up to a certain value, beyond which h remains unaltered. This assumption encompasses the differences in the release kinetics for both small and large particles. 

In conclusion, one can load drug molecules into halloysite nanotubules and get their slow release, typically during 5-30 hours. To achieve slower release kinetics, one needs a range of materials to act as stoppers on the ends of the tubules. 

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