Formulation injectates

Dilute solutions in aqueous buffers exposed to diffused or direct sunlight gave dimethylamine and 5-diazoimidazole-4-carboxamide (215). At pH 1.0 or pH 7.4 and above, this cyclized to 2-azahypoxanthine (216). In the intermediate pH range, a different product was obtained (217) which happens to be the aglycone of the antibiotic bredinin. Compound (217) was not formed by irradiation of (216). It was suggested that the betaine arose from a carbene (218) which had been quenched by water. However, (217) is colourless. Formulated injection solutions which had been found to lose activity contained 10 mg/ml... 

The most common way to formulate injections is to dissolve the drug in an aqueous vehicle. Excipients are added to control solubility, osmotic pressure, pH, stability, specific gravity, and preservation. Injections may also be formulated as oily solutions, disperse systems like suspensions and emulsions (aqueous and oily), and liposomal dispersions. Drug formulation is an essential factor in photochemical stability of the drug substance. Excipients or impurities in the formulation can also participate in photochemical reactions, leading to decomposition of the drug substance or the formulation. 

Reacting the drug with succinic anhydride results in the hemisuccinate derivative, obviously now a large 25-carbon carboxylic acid. Its solubility is less than 1 mg/ml. However, by the simple expedient of neutralizing the acidic function and forming the ionic sodium salt the solubility is increased to over 200 mg/ml. This is more than adequate to formulate injectable products of considerable concentrations. 

In the solid (crystalline) form the barbituric acid exists in the triketo or lactam form. In aqueous solution tautomerism to the enolic lactim occurs the enolic hydroxyl (at C-2) is acidic acid and is ionized according to the particular drug s pKa (e.g., pentobarbital = 8.0, phenobarbital = 7.5). Titrating such a solution with a stoichiometric equivalent of base such as NaOH will convert the lactam quantitatively to the barbiturate s sodium salt, which can be isolated. Many barbiturates are commercially produced both in the lactam and in the sodium enolate salt form. Of course, the salts are water soluble and thus are used to formulate injectable dosage forms including those for IV anesthetic use. 

The antitumor activity fME formulations of 6-MP in terms of MST, ILS, and the number of survivors on day 40 is shown in Table 9.5. The MST in mice was found to depend on two factors prolonged release of the drug from the formulation and direct interaction of tumor cells with the formulation. Thus the i.v.-i.v. and i.p.-i.p. tumor cells-formulation injection route showed greater MST and number of survivors on day 40 than the i.v.-i.p. and i.p.-i.v. injected tumor cells-formulation, respectively. There was no significant difference in MST either between the i.v.-i.v. and i.p.-i.p. or between the i.v.-i.p. and i.p.-i. V. combinations of tumor cells-formulation injection routes. The MST was found in the order Con-A-fME > PEG-fME > fME > free drug > Con-A > control (Table 9.5) in all cases, which reflected a direct correlation with the in vitro studies. The ILS was 208% to 235% with Con-A-fME. The ILS varied between 211.84% and 231.79% for PEG-fME. This shows the improved therapeutic efficacy of coated formulations. PEG-fME, however, had lower efficacy than Con-A-fME, which was due to the site specificity of the latter ligand. Also there was not much difference with respect to the route of the drug and tumor administration, as seen in case of Con-A-fME. Thus the superior activity of the PEG-coated emulsion may be due to slow and consistent release of the... 

Formulation Injection Route Number of Tumor Cells (xlO ) Normal Peritoneal Cells (xl0 )... 

Eoamable compositions in which the pressure within the cells is increased relative to that of the surroundings have generally been called expandable formulations. Both chemical and physical processes are used to stabilize plastic foams from expandable formulations. There is no single name for the group of cellular plastics produced by the decompression processes. The various operations used to make cellular plastics by this principle are extmsion, injection mol ding, and compression molding. Either physical or chemical methods may be used to stabilize products of the decompression process. 

As of 1994, there were approximately 47 progestin-containing contraceptive dmg formulations sold in the United States for use as oral contraceptives (Table 3). In addition, there are three nonoral contraceptive formulations containing progestins ie, one injectable (Depo-Provera), one as an intrauterine device (lUD) (Progestasert), and one implantable (Norplant). Of the oral formulations, all but two also contain an estrogen component, ethynylestradiol. 

Injected formulation of leuptoleine and triptoreline [57773-63 ] ate used to treat metastasized cancer of the prostrate, whereas an encapsulated formulation of bromocryptin [25614-03-3] is used to inhibit milk production in women after pregnancy. The performance of encapsulated hormonal polypeptides is weU documented (47). Injectable biodegradable mictocapsules loaded with fertUity control agents have been under development for a number of years and have been carried to various stages of clinical development (48) (see Contraceptives). 

Surfactants evaluated in surfactant-enhanced alkaline flooding include internal olefin sulfonates (259,261), linear alkyl xylene sulfonates (262), petroleum sulfonates (262), alcohol ethoxysulfates (258,261,263), and alcohol ethoxylates/anionic surfactants (257). Water-thickening polymers, either xanthan or polyacrylamide, can reduce injected fluid mobiHty in alkaline flooding (264) and surfactant-enhanced alkaline flooding (259,263). The combined use of alkah, surfactant, and water-thickening polymer has been termed the alkaH—surfactant—polymer (ASP) process. Cross-linked polymers have been used to increase volumetric sweep efficiency of surfactant—polymer—alkaline agent formulations (265). 

Most of these procedures are proprietary. Formulation development is also becoming more complex for preparation and deHvery of new vaccines. The classical vaccines are mostly prepared as injectable solutions. Aseptic techniques are required in the design and operation of the faciHties. 

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