Extended-release delivery systems

Figure 6.3. OROS-CT (Oral Osmotic System for Colon Targeting) and COER-24 (Controlled Onset Extended Release) delivery systems.

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)... 

The emergence of the concept of controlled-release delivery systems as an effective way to enhance patient compliance and extend the lifecycle of a drug has led to the need for novel ways of controlling drug-release profiles. Polymers offer the opportunity to develop functional excipients able to... 

Since the development of the Spansule brand (Smith Kline Beech am) of coated beads and granules in the late 1960s, various dmg product technologies have been developed and patented to achieve extended durations of therapeutic effects. Each of these does so by various mechanisms of control of dmg release from adrninistered dosage forms. Each method has its advantages and disadvantages, a discussion of which is available in the pharmaceutical hterature (see Drug delivery systems) (21). 

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). 

Dissolution testing has become an important component of the assessment of the quality of solid oral dosage forms and oral suspensions. The basic procedures for these oral dosage forms have been extended to transdermal delivery systems as well. The release rate for modified-release oral dosage forms adds a level of sophistication to the concept of dissolution testing, setting acceptance criteria at multiple time points. 

Most of the drug delivery systems that have been studied for clinical application are capable of rate- and/or time-controlled drug release. The therapeutic advantages in these approaches lie in the in vivo predictability of release rate, minimized peak plasma levels, predictable and extended duration of action and reduced inconvenience of frequent re-dosing and hence, improved patient compliance [1]. 

The recently introduced product Concerta is a once-a-day administration MPH delivery system called OROS (osmotically released). This delivery system creates an ascending plasma level pattern instead of the peak-and-valley pharmacokinetic profile seen in the IR preparations. Similar extended-delivery bead-technology, double-pulse preparations have been introduced for Metadate-CD at 10, 20, and 30 mg (Green-hill et ah, 2002, in press) for the spheroidal technology of Ritalin-EA, and for Adderall-XR preparations (McGough et ah, 2002, in press). Beaded stimulant preparations mix IR and delayed-release beads in a capsule. The patient can swallow the capsule whole or sprinkle the contents in food if pill taking is difficult for the child. 

Conventional systems do not offer sufficient flexibility in controlling drug-release rate and sustaining the release over time periods extending from days to months. Therefore specific modified release vaginal delivery systems are continuously under development and are based on mucoadhesive systems. Penetration enhancement may represent a necessary feature for certain delivery systems, particularly when the absorption regards a macromolecule (such as a peptide or a protein). 

Perez-Marrero R, Tyler RC. A subcutaneous delivery system for the extended release of leuprolide acetate for the treatment of prostate cancer. Expert Opin Pharmacother. 2004 5 447 157. 

Although examples of delivery systems using the parenteral and oral (solid) routes are presented in this chapter, application of dissolution controlled release matrix and coated systems concepts can extended easily (and has been) used for many other delivery routes. 

Unlike extended release parenteral formulations (depot suspensions), application of low-water-solubility salts in oral extended release forms is not used commonly. This probably is due to the fact that for oral delivery, coated and matrix-type systems are easy to design and can generate release profiles that are manipulated more easily than powder systems. Therefore, although it is not impossible, selecting a salt form with low water solubility to achieve a desired extended release profile has not been reported frequently. 

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