Controlled-release formulation

Microencapsulation of agrochemicals is mainly carried out by interfacial condensation, in situ polymerization and coacervation. Interfacial condensation [126,127] is perhaps the most widely used method for encapsulation in industry. The a.i., which 

In interfacial polymerization, the monomers A and B are polylunctional monomers capable of causing polycondensation or polyaddition reaction at the interlace [126, 127]. Examples of oil soluble monomers are polybasic acid chloride, bishalo-formate and polyisocyantates, whereas water soluble monomers can be polyamine or polyols. Thus, a capsule wall of polyamide, polyurethane or polyurea may be formed. Some trifunctional monomers are present to allow crosslinking reactions. If water is the second reactant with polyisocyanates in the organic phase, polyurea walls are formed. The latter modification has been termed in situ interfacial polymerization [128]. 

It should be mentioned that the role of surfactants in the encapsulation process is very important. Apart from their direct role in the preparation of microcapsules disper- 

There are four types of encapsulation utilizing the system of phase separation from aqueous solution [127] (i) Complex coacervation or pheise separation resulting from two oppositely charged colloids neutralizing one another, (ii) Simple coacervation where a nonelectrolyte such as alcohol causes formation of a separate polymer-rich phase, (iii) Salt coacervation where a polymer separates eis a result of a salting-out process, (iv) Precipitation and insolubilization of a polymer by changing the pH of the aqueous solution system. 

Another method that can be applied to encapsulate solid particles is a modification of the coacervation process described above. In this method a technique of solvent evaporation is used to precipitate the polymers as intact coatings. The solid particles are suspended in a solvent solution of the polymer and emulsified into a liquid. The emulsion is then heated to evaporate the solvent causing the polymer to insolubilize as a coating around the suspended particles. Alternatively a nonsolvent for the polymer is added to the suspension of particles in polymer solution, causing the solvent to phase separate and the polymers to insolubilize to coatings 

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Potential antidepressant activity of lusaperidone (14) and its derivatives were investigated on al, q 2A, q 2B and q 2C receptor binding tests (00BMCL71). Hydrophilic controlled release formulations of 14 were developed and patented (00MIP8). 

The acyl groups introduced included 4-phenylbenzoyl, phenylacetyl, 4-methoxybenzoyl, acetyl, 2,4-dichlorophenoxyacetyl, and 2,2-dichloropro-pionyl. Introduction of the last pair of acyl groups is important because they are bioactive (insecticides), i.e., the product can be employed in controlled-release formulations [159]. The structures of all these esters were determined by FTIR and NMR spectroscopy, whereas their solution properties, includ-... 

Occasionally in the synthesis of the copolymers, insoluble material is produced. This results from polymer containing blocks of polyglycolide rather than the desired random structure. Obviously, such compositions would have considerable effect on the performance of controlled release formulations utilizing those polymers. This problem is particularly evident when one is seeking to utilize the 50 50 glycolide/lactide copolymer as a biodegradable excipient. However, with carefully controlled polymerization conditions, useful 50 50 polymer is readily produced. 

The earlier work of Miller (35), Outright (37), and Brady (5) on nonmedicated implants provided an excellent basis for further studies on specific controlled release formulations such as the determination of the biodegradation rates of lactide/glycolide drug-loaded microspheres (38). Those studies were done with l c-iabeled polymers produced from DL-lactic acid and glycolide. The final formulations tested in rats were microspheres loaded with H-labeled steroid and polymer as the matrix. The microspheres were administered intramuscularly and animals were serially sacrificed over a period of about a year. 

Developers of controlled release formulations have employed polymers produced from both L-lactide and Dl -lactide. In terms of clinical studies, however, it appears that perhaps the DL-lactide formulations have been somewhat more successful. It is unclear if this is due to the DL-lactide materials being less crystalline and more permeable to most drugs or perhaps more sophisticated techniques and... 

Microspheres and microcapsules of lactide/glycolide polymers have received the most attention in recent years. Generally, three microencapsulation methods have been employed to afford controlled release formulations suitable for parenteral injection (1) solvent evaporation, (2) phase separation, and (3) fluidized bed coating. Each of these processes requires lactide/glycolide polymer soluble in an organic solvent. 

The rate and duration of steroid release is affected by (1) polymer composition, (2) drug/polymer ratio (3) microsphere size distribution, and (4) microsphere quality (75). The ratio of glycolide to lactide in the copolymer has been found to be more dominant than the polymer molecular weight in the design of controlled release formulations. Microspheres of smaller size provide in vivo drug profiles of higher levels and shorter durations because of greater surface area. 

Calcitonin, LHRH, lypressin, and somatostatin have been formulated in lactide/glycolide copolymers as injectable, controlled release formulations (117). Various agonistic and antagonistic analogs have been studied. Generally these compounds are hydrophilic polypeptides,... 

Nelson, J.H., D.L. Stonebumer, E.S. Evans, Jr., N.E. Pennington, and M.V. Meisch. 1976. Diatom diversity as a function of insecticidal treatment with a controlled-release formulation of chlorpyrifos. Bull. Environ. Contam. Toxicol. 15 630-634. 

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative colitis and Crohn s disease and are used in moderate to severe disease. Prednisone is most commonly used. Budesonide is an oral controlled-release formulation that minimizes systemic effects. 

Sol-gel microencapsulation in silica particles shares the versatility of the sol-gel molecular encapsulation process, with further unique advantages. Sol-gel controlled release formulations are often more stable, potent and tolerable than currently available formulations. The benefits of microencapsulation can be customized to deliver the maximum set of benefits for each active ingredient. Overall, these new and stable combinations of active pharmaceutical ingredients (APIs) result in improved efficacy and usability. 

Controlled release formulations, 7 551 pesticide formulations, 7 551-553 Controlled rheology, 14 275 Controlled stress viscometers, 21 736-737 Controlled structure polymeric betaines, 20 481... 

Loss of Tin. The preparation and characterization of organ-otin-epoxy polymers have been reported earlier (3). In an effort to determine the loss of tin from these controlled release formulations, 0.5-mm thick coatings were kept immersed in 4% sodium chloride solution under conditions approximating Figure 2a. The concentration of TBTC1 in the aqueous phase was maintained low by continuously extracting it into hexane. Analysis of the coating at the end of 16 months revealed that not more than 2% tin was lost in any of the four cases studied. 

Sugawara M, Kadomura S, He X, Takekuma Y, Kohri N, Miyazaki K (2005) The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations. Eur J Pharm Sci 26 1-8. 

Extended drug effect can be maintained with controlled release formulations. 

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. 

Another aspect related to control release of drugs concerns the type of structures that currently appear to be working. Not unexpectedly, because of compatibility and degradation purposes, most of the effort on the control release formulations includes polymers that have both a hydrophobic and hydrophilic portion with the material necessarily containing atoms in addition to carbon. Another concern is that the products of degradation are not toxic or do not form toxic materials. It has also been found that amorphous materials appear to be better since they are more flexible and permit more ready entrance of potential degrad-ative compounds. 

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