Oral delivery systems, controlled-release

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

Modi NB, Wang B, Noveck RJ, et al Dose-proportional and stereospecific pharmacokinetics of methylphenidate delivered using an osmotic, controlled-release oral delivery system. J Clin Pharmacol 40 1141-1149, 2000h... 

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 ... 

Baluom, M., M. Friedman, and A. Rubinstein. 2001. Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems. J Control Release 70 139. 

H. G. Zerbe and M. Krumme. Smartrix system Design characteristics and release properties of a novel erosion-controlled oral delivery system, in Michael J. Rathbone, Jonathan Hadgraft, and Machael S. Roberts (eds.), Drugs and the Pharmaceutical Sciences, vol. 126 Modified-Release Drug Delivery Technology. New York Marcel Dekker, 2003, pp. 59-76. 

A. Gazzaniga, M. E. Sangalli, G. Maffione, and P. Iamartino, Time-dependent oral delivery system for colon-specific release, Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 20 318-319 (1993). 

Sangalli, M.E.,Maroni, A., Zema, L., Busseli, C., Giordano, F., and Gazzaniga,A. (2001), In vitro and in vivo evaluation of oral system for time and/or site specific drug delivery, J. Controlled Release, 73,103-110. 

Shah A, Britten NJ, Olanoff LS, Badalamenti JN. Gel-matrix systems exhibiting bimodai controlled release for oral delivery. J Control Rel 1989 9 169-75. 

Sajeesh S, Bouchemal K, Marsaud V et al (2010) Cyclodextrin complexed insulin encapsulated hydrogel microparticles an oral delivery system for insulin. J Control Release 147(3) 377-384... 

Drug delivery systems of once-daily products (Concerta, Metadate CD, Ritalin LA, Adderall XR) provide 8 to 12 hours of symptom control. Concerta uses an oral osmotic (OROS) controlled-release delivery system, while other preparations use combinations of immediate-release or extended-release beads containing drug. Concerta is a nondeformable tablet and it should not be given to children with gastrointestinal narrowing due to the risk of obstruction. Older wax-matrix sustained-release products (e.g., Ritalin SR)... 

Boston, Ma., March 1999, p.252. 012 CONTROLLED-RELEASE ORAL DELIVERY SYSTEMS Fix A... 

The pH-sensitive hydrogels have been most frequently used to develop controlled release formulations for oral administration. The pH in the stomach (<3) is quite different from the neutral pH in the intestine, and such a difference is large enough to elicit pH-dependent behavior of polyelectrolyte hydrogels [95]. These hydrogels have been investigated in a number of therapeutic oral delivery systems either as... 

Risperidone free base preparations include film-coated tablets (1, 2, 3, 4 and 6 mg), orodispersible tablets (0.5, 1, 2, 3 and 4 mg), liquids at 1 mg/mL and depot preparations. Paliperidone is available as free base tablets (3, 6 and 9 mg), the hexadecanoate (palmitate) and extended release formulation using an osmotic-controlled release oral delivery system. 

Historically, the oral route of administration has been used the most for both conventional and novel drug-delivery systems. There are many obvious reasons for this, not the least of which would include acceptance by the patient and ease of administration. The types of sustained- and controlled-release systems employed for oral administration include virtually every currently known theoretical mechanism for such application. This is because there is more flexibility in dosage design, since constraints, such as sterility and potential damage at the site of administration, axe minimized. Because of this, it is convenient to discuss the different types of dosage forms by using those developed for oral administration as initial examples. 

---