Biphasic delivery

Baca-Estrada, M. E., et al.. Effects of lL-12 on immune responses induced by transcutaneous immunization with antigens formulated in a novel lipid-based biphasic delivery system. Vaccine, 18, 1847-54, 2000. 

Hormones, proteins, and small peptides are not suitable for oral administration without complex modifications in the formulation. A variety of approaches for insulin delivery, as a model drug, have been attempted to improve on its bioavailability. Advances have been realized in the delivery of insulin through oral, nasal, rectal, dermatologic, and ocular routes. Proteins can also be delivered transdermally, using a lipid-based, biphasic delivery system in therapeutic quantity. 

Proteins can also be delivered transdermally using a lipid-based biphasic delivery system in therapeutic quantity. Insulin treatment (10-50 mg/g formulation) was administered by a transdermal patch adhered to the abdomen of anesthetized Sprague-Dawley rats made diabetic by a single injection of strep-tozotocin (55 mg/kg). Blood was sampled from a tail vein every 2-4 h for 48 h. Response to transdermally applied insulin was both pH and concentration dependent. Blood glucose was decreased by 55% in the treated animals with mean response duration of 15 h. Serum insulin level was 162 pg/mL. 

Constant release is not always the desired solution for controlled drug administration some therapeutic situations require consecutive pulses. A biphasic oral delivery system able to release an immediate dose of therapeutic agent as well as a further pulse of drug after some hours would, useful. In order to obtain such a desired release performance, a new system (three-layer tablet) has been designed with the following characteristics ... 

Lenaerts et al. (2) prepared a biphasic drug delivery device for tramadol consisting of polyvinyl acetate and polyvinylpyrrolidone having a sustained release for 24 hours. Polyvinylpyrrolidone was also used by Midha et al. (3) in the trans-dermal delivery of atomoxetine. 

Timmins, P., Dennis, A. B., and Vyas, K. A. Biphasic controlled release delivery system for high solubility pharmaceuticals and method, U.S. Patent 6,475,521, 2002. 

Gallo-Penn, A. M., Shirley, P. S., Andrews, J. L., Tinlin, S., Webster, S., Cameron, C., Hough, C., Notley, C., Lillicrap, D., Kaleko, M. and Connelly, S. (2001). Systemic delivery of an adenoviral vector encoding canine factor VIII results in short-term phenotypic correction, inhibitor development, and biphasic liver toxicity in hemophilia A dogs. Blood 97, 107-113. 

In biphasic reactors or two-phase partitioning bioreactors (TPPB), the substrate is located mostly in the immiscible phase and diffuses to the aqueous phase. The enzyme catalyzes conversion of the substrate at the interface and/or in the aqueous phase. The product/s of the reaction then may partition to the organic phase. The system is self-regulated, as the substrate delivery to the aqueous phase is only directed by the partitioning ratio between the two phases and the enzymatic reaction rate [53]. The use of ionic liquid/supercritical carbon dioxide for enzyme-catalyzed transformation is gaining attention [69]. 

Misra, A., et al. (1997), Biphasic testosterone delivery profile observed with two different transdermal formulations, Pharm. Res., 14(9), 1264-1268. 

King, M. I, et al. (2002),Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats, Diabetes Technol. Ther., 4(4), 479 188. 

Ofori-Kwakye K, Fell JT. Leaching of pectin from mixed films containing pectin, chitosan and HPMC intended for biphasic drug delivery. Int J Pharm 2003 250(1) 251-257. 

DL Theis, LJ Lucisano, GW Halstead. Use of stable isotopes for evaluation of drug delivery systems Comparison of ibuprofen release in vivo and in vitro from two biphasic release formulations utilizing different rate-controlling polymers. Pharm Res 11 1069—1076,1994. 

Bajwa, G.S., Hoebler, K., Sammon, C., Timmins, P. and Melia, C.D. (2006) Microstructural imaging of early gel layer formation in HPMC matrices. J Pharm Sci, 95, 2145-2157. Timmins, R, Dennis, A.B. and Vyas, K.A. (2002) Biphasic controlled release delivery system for high solubUity pharmaceuticals and method. US Pat. 6,475,521. 

Timmins, R, Dennis, A.B. and Vyas, K.A. (2003) Method of use of a biphasic controlled release delivery system for high solubUity pharmaceuticals and method. US Pat. 6,660,300. 

Apparatus The interfadal synthesis reactions described below are each carried out batchwise under mild reaction conditions (<70 C and 1 atm) in a three-necked, 585-mL Morton-fiask reactor that has the following provisions (4-6) (1) a Teflon seal joint that permits the insertion and free rotation of the shaft of a mechanical stirrer through the middle neck of the reactor while keq >ing the reactor air-tight (2) introduction of the biphasic reaction mixture and delivery of a gaseous reactant through a stoppered side neck (3) catalyst addition through the other, sq>tumed side neck and (4) temperature control by a thermostated water bath. 

Interestingly, Quarles found osteoblast cells in culture required serum for complete mitogenic action (Quarles et al. 1991). While he considered that this might be to trigger the signal transduction pathway (e.g., PTH contamination) an alternative possibility is that Tf inclusion in serum improved Al delivery to its intracellular site of action. Al modulation of G protein function is an attractive theory for the biphasic mechanism(s) of mitogenic action and inhibition (see Sect. G), particularly since Al could act alone or combined with F to have differing effects. 

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