Carbomate

The stereospecificity of the methylene transfer provides compelling support for a concerted mechanism and this conclusion has rarely been disputed. It is instructive, however, to review the experimental evidence that allowed for the elimination of the alternative mechanistic proposals, namely, a radical addition and a carbome-tallation (Scheme 3.4). 

SpUl-schwelung, /, low-temperature carbom za-tion with gas recirculation, -topf, m. rinsing pot, rinsing jar. -trog, m. rinsing trough. 

Liquids made of ions Usually when we think of ionic compounds, we think of solids- sodium chloride magnesium sulfate lithium carbom... 

A urethane is a carbonyl-containing functional group in which the carbom 1 carbon is bonded to both an —OR group and an -NR2 group. As such, a urethane is halfway between a carbonate and a urea. 

The viscosity of an emulsion can be of crucial importance for its stability, especially the viscosity of the external phase. A high viscosity reduces creaming and also lessens the tendency of particles to coalescence and produce phase separation. Examples of the widely used viscosity-imparting agents are alginates, bentonite, carboxymethylcellulose, polyvinyl pyrrolidone, hydroxypropylcellulose, and carbomer. 

Acacia Ailgnic acid Bentonite Calcium carbonate Carbomer... 

The carbomer polymeric gel base itself has been used successfully to treat moderate to severe cases of dry eye (keratoconjunctivitis sicca) [282]. The dry eye syndrome is usually characterized by deficiency of tear production and, therefore, requires frequent instillation of aqueous artificial tear eyedrops to keep the corneal epithelium moist. The gel base applied in a small amount provides a prolonged lubrication to the external ocular tissues, and some patients have reduced the frequency of dosing to control their symptoms to three times a day or fewer. 

There are two EPARs for eyedrops. Specific issues considered for these include container composition and tamper evidence, the optimization of the formulation and manufacture, preservative and preservation issues, and justification for the use of nonterminal sterilization processes. Many of the points concerning active ingredients and excipients are similar to those discussed above. Changes in formulation during the development process (e.g., for carbomers or surfactants) are mentioned. Particle size controls for suspension products are discussed. 

Borchard, G. LueBen, H.L. deBoer, A. G. Verhoef, J. C. Lehr, C.-M. Junginger, H.E., The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. Ill Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro, j. Control. Rel. 39, 131-138 (1996). 

LueBen, H.L., Verhoef, J.C., Borchard, G., Lehr, C.-M., De Boer, A.G., and Junginger, H.E., Mucoadhesive polymers in peroral peptide drug delivery. II. Carbomer and polycarbophil are potent inhibitors of the intestinal proteolytic enzyme trypsin, Pharm. Res., 12 1293-1298 (1995). 

A novel concept of using bioadhesive polymers as enzyme inhibitors has been developed [97]. Included are derivatives of poly acrylic acid, polycarbophil, and car-bomer to protect therapeutically important proteins and peptides from proteolytic activity of enzymes, endopeptidases (trypsin and a-chymotrypsin), exopeptidases (carboxypeptidases A and B), and microsomal and cytosolic leucine aminopeptidase. However, cysteine protease (pyroglutamyl aminopeptidase) is not inhibited by polycarbophil and carbomer [97]. 

Generally the functional groups in 28 do not interfere in the silylformylation to afford 29 (Tab. 6.3), for example, 28 having hydroxy, p-tosylamino and carbomate... 

Chatani s proposed mechanism bears some similarity to that of Jun s reaction (Scheme 9.12). They both begin with hydroamination of the C=C 7t-bond of a rhodium vinylidene. The resultant aminocarbene complexes (71 and 62) are each in equilibrium with two tautomers. The conversion of 71 to imidoyl-alkyne complex 74 involves an intramolecular olefin hydroalkynylation. Intramolecular syn-carbome-tallation of intermediate 74 is thought to be responsible for ring closure and the apparent stereospecificity of the overall reaction. In the light of the complexity of Chatani and coworkers mechanism, the levels of chemoselectivity that they achieved should be considered remarkable. For example, 5 -endo-cyclization of intermediate 72 was not observed, though it has been for more stabilized rhodium aminocarbenes bearing pendant olefins [27]. 

In this study, the influence of several formulation factors on the release kinetics of potassium chloride from directly compressed matrices is investigated. Formulations containing hydrophilic (methylcellulose, carbomer), plastic (polyvinyl chloride) and wax (glycerol palmitostearate) matrix materials at concentrations of 10%, 15% and 20%, and insoluble excipients, were prepared and tested using the USP XXI-NF XVI rotating paddle method. 

Hardness had no marked effect on release characteristics except for wax matrices. With hydrophilic matrices, for methylcellulose, increased matrix material concentration did not affect the release profile, but for carbomer, as the concentration increased, a significant decrease in released amount was obtained. 

Fig. 1—Potassium chloride release profiles from sustained release matrix tablets (hardness, 7.5-8 kp) 10% ( ), 15% ( ), 20% ( ) carbomer 10% ( ), 15% (o), 20% (V) methylcellulose.

The results of the release experiments are summarized in Fig. 1 and Fig. 2, which represent the percentage released as a function of time. As expected, the drug was released from tablets more slowly with an increase in polymer content. When 10%, 15% and 20% of carbomer were incorporated into the formulations (Fig. 1), the amount of potassium chloride decreased from 93% to 84-7% and 77.3% respectively at the end of 3 h. Glycerol palmitostearate showed similar results for the concentrations of 10%, 15% and 20%, i.e. the amount released was decreased, in 3 h, from 75.7% to 71.4% and 64.9% respectively (Fig. 2). Similar results were also obtained for polyvinyl chloride and methylcellulose. Carbomer and polyvinyl chloride matrix tablets show an... 

The goodness of fit was evaluated by the residuals and correlation coefficients are given in Table 3. For polyvinyl chloride, glycerol palmitostearate, carbomer and methylcellulose matrix tablets, equation (4) showed a significantly better fit than equations (2) and (3) by the / test. 

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