Controlled-release preparations, modified

Modified Lignins as the Carriers for Controlled Release Preparations... 

Zentner and coworkers [24,26] utilized this information in their development of a system that releases this drug over a 24 hr period. The use of NaCl to modulate the release of diltiazem presents an interesting problem in that the concentration of the solubility modifier must be maintained within certain limits and below its saturation solubility within the device. To solve this problem, core formulations were developed that contained both free and encapsulated NaCl. The encapsulated NaCl was prepared by placing a microporous coating of cellulose acetate butyrate containing 20 wt% sorbitol onto sieved NaCl crystals. The coated granules released NaCl over 12-14 hr period via an osmotic mechanism into either water or the core tablet formulation. The in vitro release profile for tablets (core I devices) containing 360 mg of diltiazem HC1 and 100 mg of NaCl equally divided between the immediate release and controlled release fractions... 

Modified caprolactone monomer polymers, (I), were prepared by Chen et al. (3) and then converted into biodegradable polymers and used in the controlled release of pharmaceutical agents. 

Buccoadhesive-controlled release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP) and compared to those prepared with PVP, PVA, HPMC, and acacia by a modified tensiometry method in vitro. It was found that the adhesion force was significantly affected by the mixing ratio of CP CMC in the tablets. CMC is necessary for controlling the release rate, whereas CP is important in providing bioadhesion. The tablets containing 15% CMC and 35% CP were found to have optimum drug release rate and bioadhesion [81]. 

Lin, W., Garnett, M. C., Davis, S. S., Schacht, E., Ferruti, P., and Ilium, L. (2001), Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles, J. Controlled Release, 71(1), 117-126. 

Soppimath KS, Kulkarni AR, and Aminabhavi TM. Chemically modified polyacrylamide-g-guar gum-hased cross-linked anionic microgels as pH-sensitive dmg delivery systems Preparation and characterization. Journal of Controlled Release 2001 75 331-345. 

Consider the formulation Osmosin was a modified release preparation of indomethacin. It was designed to release the active drug under osmotic control. Instead it allowed its potassium content to be released in a way that caused perforation of the small bowel distal to the duodenum. The drug provides an example of the formulation causing the problem, and the drug serves as a reminder that consideration needs to be given to the formulation as a possible cause of trouble which can be remedied by reformulation. 

Drug release should be controlled in accordance with the therapeutic purposes and pharmacological properties of the active substances. The plasma drug levels-time profiles after oral administration can be classified as ratetime-controlled release. Rate-controlled release is further classified into three types, i.e. immediate-release, prolonged-release, and modified-release. One typical time-controlled release is delayed-release. More advanced releases can be achieved by combinations of these different release types (Fig. 14.9). Various CyD derivatives have been used in order to modify drug releases in oral preparations [13, 15]. 

Diltiazem. In a placebo-controlled study in 12 healthy subjects diltiazem 60 mg three times daily was given to 12 healthy subjects for 7 days, with ranolazine 240 mg three times daily on days 4 to 7. Ranolazine did not alter the pharmacokinetics of diltiazem, but diltiazem increased the AUC and maximum plasma level of ranolazine by 85% and twofold, respectively. A further study using modified-release diltiazem 180 mg, 240 mg, and 360 mg once daily, and a slow-release preparation of ranolazine 1 g twice daily, resulted in increases in the AUC of ranolazine of 52%, 93%, and 139%, respectively. ... 

Microsphere beads were prepared with alginate-derived polymeric surfactants in aqueous solution of sodium and calcium chloride [33]. Ibuprofen, a hydrophobic drug, was loaded on the modified alginate beads and the in vitro control release was studied. It was found that drug loading level was higher than those obtained for unmodified alginated with a well controlled release rate [33]. 

Velezheva and coworkers described the Lewis acid-catalyzed Nenitzescu indolization using zinc iodide in dichloromethane (Scheme 9, equation 1 and 43-45) [23], later improved to the use of zinc chloride (equations 2, 3) [24]. Boruah and colleagues employed a Lewis acid-catalyzed microwave-modified Nenitzescu indolization to prepare 3-amino-5-hydroxybenzo[ ]indoles (Scheme 9, equation 4, and 46-47) [25]. Boron trifluoride etherate was superior to other Lewis adds studied (TiCl, AICI3, ZnClj, InCy. The reaction presumably proceeds by a Michael addition of the carbonyl component, in the form of a p-hydroxyenamine to the naphthoquinone, and the urea serves as a controlled-release source of ammonia. 

The W-acetyl chitosans are the most interesting for controlled release. Galactosylated chitosan microspheres have been prepared. Production of more specific oligoglycoside-chain chitosan might develop into active targeting of specific tissues. Pectinate gel beads modified with trimethyl chitosan have been prepared and evaluated for colon targeted delivery of macromolecules. 

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