Procaine preparations

Monoamine oxidase inhibitors and many pharmacological agents are synergistic, sometimes resulting in a hypertensive crisis. The agents with which the MAOIs may be synergistic include amphetamine, dextroamphetamine, methyl amphetamine, ephedrine, procaine preparations (which usually contain norepinephrine), epinephrine, methyldopa, and phenylpropanolamine (over-the-counter cold preparations). 

Preparation of the prototype in this series, procaine (31). i.irts with the oxidation of p-nitrotoluene (27) to the corre-Hiding benzoic acid (28). This is then converted to the acid ll Inride (29) reaction of the halide with diethyl aminoethanol fiI lords the so-called basic ester (30). Reduction by any of a .fl ics of standard methods (e.g., iron and mineral acid, cata-Ivlic reduction) affords procaine (31). ... 

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

Two basic methods are used to prepare parenteral suspensions (a) sterile vehicle and powder are combined aseptically, or (b) sterile solutions are combined and the crystals formed in situ. Examples of these procedures may be illustrated using Penicillin G Procaine Injectable Suspension USP and Sterile Testosterone Injectable Suspension USP. 

Procaine which is a synthetic preparation in powder form used... 

TRXF was used to determine the trace elements in samples of lecithin, insulin, procaine, and tryptophan in an attempt to develop elemental fingerprints that could be used to determine the origin of the sample [80]. It was reported that through the use of matrix-independent sample preparation and an internal standard, one could use TXRF to facilitate characterization of the samples without the need for extensive pretreatment. In another work, a study was made of the capability of TXRF for the determination of trace elements in pharmaceutical substances with and without preconcentration [81]. 

In order to make isotonic solution, 0.6 g of procaine hydrochloride is dissolved in purified water to make 14 mL of an isotonic solution, and the preparation is adjusted to a volume of 60 mL by adding isotonic vehicle such as NSS (normal saline solution). 

The preparation and anaesthetic properties of some (N,N-Dialkyl-amino)-alkyl-3-thienylsulfide hydrochlorides were studied 36). As local anaesthetics they were found, in preliminary examinations, to be equal to or better than procaine in activity in the guinea pig test. In addition it was found that the alkaminoesters of phenyl-3-thienylglycolic... 

Procaine can be prepared by one of three main routes, the basic pathways of which are illustrated in the three Schemes which follow [1-4,11]. 

The United States Pharmacopoeia describes the following two identification tests for procaine [31]. In one, the infrared absorption spectra of standard and sample in KBr pellets are compared, and require to exhibit maxima only at the same frequencies. In another test, 10 mg of drug is dissolved in 1 mL of water, to which is added 1 drop each of hydrochloric acid and 1 10 sodium nitrite solution. One then adds 1 mL of a solution prepared by dissolving 0.2 g of 2-naphthol in 10 mL of 1 10 sodium hydroxide solution, shakes, and obtains a scarlet-red precipitate as a positive reaction. 

Shoukry et al. have prepared plastic membrane ion-selective electrodes for the determination of procaine and other anaesthetic compounds [69]. The electrode selective for procaine was prepared with the use of a membrane containing 15% of the procaine tetraphenylborate ion pair with 40% of dioctyl phthalate and 45% of poly vinyl chloride (PVC). The membrane was attached as a disc (12 mm diameter, 0.3 mm thick) to the polished PVC cap of the electrode tube, which contained an internal solution of 0.1 M sodium chloride made 1 mM in the same drug, and in contact with a Ag-AgCl wire. Linear response ranges were determined to be 20.0 pM to 16 mM for procaine over the pH range of 3.1 to 7.9. The electrodes could also be used in the potentiometric titration of the drug with 0.01 M sodium tetraphenylborate. 

Liu et al. prepared a procaine-sensitive FET transducer by coating a suitable electrode with sodium tetraphenylborate-procaine active material, 5% of poly(vinylchloride), and dibutyl phthalate in tetrahydrofliran [71]. The optimum operating pH was determined to be between 2 and 7. The transducer was applied in the potentiometric titrimetric determination of procaine in injection solution, where the recovery was 100.7% and the coefficient of variation (n = 2) was 1.4%. 

Satake et al. reported the use of a coated wire electrode sensitive to procaine and other local anesthetic cations, and their application to potentiometric determination [73]. Electrodes were constructed from a copper wire (0.8 mm diameter), coated with a PVC membrane comprising a mixture of the drug-tetraphenylborate ion-pair, dioctyl phthalate, polyvinyl chloride, and tetrahydrofuran. Potential measurement was made with respect to a Ag-AgCl reference electrode. The electrodes showed linear responses with a Nemstian slope for procaine over the concentration range investigated. The method was used for analyses of the drug in pharmaceutical preparations. 

Hamada et al. used a poly (vinyl chloride) matrix membrane ion-selective electrode for the analysis of procaine [76]. Procaine flavianate (10 mg, prepared by precipitation from an equimolar mixture of procaine hydrochloride and flavianic acid), was mixed with PVC powder (150 mg), dioctyl phthalate (370 mg), and tetrahydrofuran (4 mL). This mixture was used to produce membranes (3 cm diameter), from which discs were cut to prepare ion-selective electrodes. The electrodes were used in conjunction with a double-junction Ag-AgCl (KNO3) reference electrode for the potentiometric determination of procaine hydrochloride at 25°C. 

Wang has determined procaine hydrochloride in the presence of citric acid [82]. To the sample (prepared as 5 mL of aqueous solution) were added 5 mL of water, 1 mL of 0.1 M hydrochloric acid, and 200 mg potassium bromide. The resulting solution was titrated with 0.1 M sodium nitrite, ultimately yielding the total content of procaine hydrochloride and citric acid. 

Liu et al. have reported the development and applications of the commonly used local anaesthetic sensitive field-effect transistor(FET) [56]. The ion-pair complexes of procaine with silicotungstate, tetraphenylborate, or reineckate were prepared as electroactive materials for a drug sensor. These active materials were coated onto the platinum draw wire of a MOSFET to make a local anaesthetic-sensitive FET that... 

Ogurtsov and Yavors ka have used polarogr hy to determine procaine in suppositories and in "Menovasin" preparation [60]. A portion of an aqueous extract of the suppository, or a portion of the liquid "Menovasin" preparation, was mixed with 10 mL of 0.1 M LiCl, and diluted to 25 mL... 

Nikolic et al. reported the preparation and coulometric determination of quaternary ammonium iodides of procaine and of other local anesthetics [63]. After extraction from 0.33 M NaOH, the quaternary iodide salts were prepared by precipitation with methyl iodide in ethyl ether. The quaternary iodides were then coulometrically determined with the use of a Radiometer titrator. The method used a silver cathode and anode (in electrolytes of 2 M and 0.4 M H2SO4, respectively), and a reference mercurous sulfate electrode. For drug determinations in the range of 0.12 to 0. 96 mg, the standard deviations were typically found to be 4 to 8 pg. 

Carmona et al. described a simple and rapid kinetic spectrophotometric method for the determination of procaine in pharmaceutical preparations [35]. The method was applied to the determination of the drug in various pharmaceutical samples. 

Salama and Omar have described a rapid, specific, and convenient colorimetric method for the determination of procaine hydrochloride in pharmaceutical preparations [40]. The method is based on an intensity measurement of the orange-red color developed when the drug is allowed to react with l,2-naphthoquinone-4-sulfonic acid (sodium salt) in an aqueous solution. The method is suited for routine analysis of official preparations of procaine. 

Montero et al. reported an indirect atomic absorption spectrometric method combined with a flow-injection precipitation technique for the determination of procaine in pharmaceutical preparations [53]. The precipitate formed by the injection of Co(II) into a sample stream containing 10 to 110 pM procaine at pH 8.0 to 9.1 was retained on a stainless steal filter, and analyzed at 240.7 nm by an online atomic... 

Mikami et al. have described a rapid liquid chromatography method for the determination of procaine and other drugs in pharmaceutical preparations [145]. The separation is effected using a Wakosil-5 C,g column. The mobile phase consisted of aqueous acetonitrile -triethylamine in various ratios, or of 30% or 50% aqueous acetonitrile. Detection was based on the ultraviolet absorption at 225 to 265 nm, and method recoveries from dosage forms were in the range of 98.5 to 100.3%. 

Klein reported the use of a quantitative and qualitative determination of procaine in pharmaceutical preparations by capillary isotachophoresis [149]. 

Detection was effected with a conductivity detector. The method was used to determine procaine in mass-produced suppositories and ointments, and in locally prepared pharmaceutical solutions. The results were found to agree with those obtained using either spectrophotometry or polarography. 

Varea et al. described a study of the stability of procaine hydrochloride in cardioplegie solutions, prepared from Ringer s solution and electrolytes (both un-buffered, or buffered with sodium bicarbonate) [156], The content of the drug was measured by ultraviolet speetrophotometry, and the was found to follow pseudo-first order kinetics. The stability of the drug entity in buffered solutions was estimated to be approximately 5-7 days. 

The site of drug action means where a drug acts and mechanism means how the drug acts. Drug which act only at the site of application (i.e. localized region) are termed as local or topical action for example, ointments, paste, creams and certain other local preparations used externally produce only local effect. The local anaesthetics like lignocaine, procaine produce anaesthesia (local) in a localized region only. 

The activity of penicillin G was originally defined in units. Crystalline sodium penicillin G contains approximately 1600 units per mg (1 unit = 0.6 meg 1 million units of penicillin = 0.6 g). Semisynthetic penicillins are prescribed by weight rather than units. The minimum inhibitory concentration (MIC) of any penicillin (or other antimicrobial) is usually given in mcg/mL. Most penicillins are dispensed as the sodium or potassium salt of the free acid. Potassium penicillin G contains about 1.7 mEq of K+ per million units of penicillin (2.8 mEq/g). Nafcillin contains Na +, 2.8 mEq/g. Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for years at 4°C. Solutions lose their activity rapidly (eg, 24 hours at 20°C) and must be prepared fresh for administration. 

Obviously, very little is known about illicit preparations since the major specification is minimal cost and manufacturing convenience. Heroin, for example, has been diluted with quinine, procaine, lactose, and many other excipients. To be safe, the chemist should regard such samples as completely unknown and not assume that the excipients will be innocuous to the chromatographic system. One important precaution is to anticipate contamination and impurities. The former may not be present uniformly per sample weight while the latter will likely be uniform. 

Procaine salts and benzathine salts of penicillin G provide repository forms for intramuscular injection. In dry crystalline form, penicillin salts are stable for long periods (eg, for years at 4 °C). Solutions lose their activity rapidly (eg, 24 hours at 20 °C) and must be prepared fresh for administration. 

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