Release, drug formulation controlled

Roston, D.A. Sun, J.J. Collins, P.W. Perkins, W.E. Tremont, S.J. Supercritical fluid extraction-liquid chromatography method development for a polymeric controlled-release drug formulation. J. Pharm. Biomed. Anal. 1995, 13 (12), 1513-1520. 

Controlled-release drug formulation Dried blood... 

Miscibility of Polymers in Binary Fluid Mixtures. Cellulose Derivatives. Miscibility of cellulose derivatives in binary fluid mixtures of carbon dioxide is of recent interest because of the significance of these polymers in controlled-release drug formulations, and also because of the traditional significance of cellulose based polymers as film or fiber... 

Details are given of the synthesis of a new family of ether-anhydride copolymers for use in controlled release drug formulations for inhalation. Microparticles containing model drugs were made with sizes suitable for deposition in various regions of the lung following inhalation as a dry powder. 50 refs. 

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. 

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

The sample must be soluble If it s not in solution, it cannot be analyzed by HPLC. Although this may seem obvious, solubility issues complicate real assays of low-solubility drugs and controlled-release formulations. Many situations encountered in pharmaceutical analysis, such as low recovery, lack of mass balance, and out-of-specification results, might stem from solubility problems in a sample preparation step, rather than the HPLC analysis itself. 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

Another strategy rehes on the strong peristaltic waves in the colon that lead to a temporarily increased luminal pressure (pressure-controlled drug release). Pressure-sensitive drug formulations release the drug as soon as a certain pressure limit is attained, i.e. destruction force is exceeded. 

The inert matrix formulation provided by ethylcellulose and Pevikon (polyvinyl chloride) was an effective vehicle for controlled release drug delivery systems. 

Budesonide is a potent synthetic analog of prednisolone that has high affinity for the glucocorticoid receptor but is subject to rapid first-pass hepatic metabolism (in part by CYP3A4), resulting in low oral bioavailability. A controlled-release oral formulation of budesonide (Entocort) is available that releases the drug in the distal ileum and colon, where it is absorbed. The bioavailability of controlled-release budesonide capsules is approximately 10%. 

Oxycodone is a semisynthetic opioid derived from thebaine and used for oral pain relief. It is commonly formulated as an immediate-re lease medication with acetaminophen or aspirin. A con-trolled-release oxycodone formulation is used for the treatment of moderate to severe pain it provides controlled drug delivery over 12 h. The oral bioavailability of this formulation is 60 to 87%.35 The results of clinical studies of patients with postoperative and cancer pain show that oxycodone has a potency 1.5 times that of morphine. 

An NDA can be submitted for a previously unapproved new molecular entity, or for a new salt, new ester, prodrug, or other noncovalent derivative of a previously approved new molecular entity, formulated as a modihed-release drug product. The first modified-release drug product for a previously approved immediate-release drug product should be submitted as an NDA. Subsequent modified-release products that are pharmaceutically equivalent and bioequivalent to the listed drug product should be submitted as ANDAs. BA requirements for the NDA of an extended-release product are listed in 320.25(f). The purpose of an in vivo BA study for which a controlled-release claim is made is to determine if all of the following conditions are met. 

The controlled release device consists of a thin drug formulation-agarose gel supported on an impermeable backing material. A number... 

---