Comparative studies on the in vitro drug dissolution profiles for hydroxyzine hydrochloride tablets.

OBJECTIVE: A significant practical problem in the standardization of dissolution testing is addressed. In vitro releasing characteristics of hydroxyzine hydrochloride tablets are presented to further the documentation of bioequivalency criteria. DESIGN: The assessment model compares the official United States Pharmacopeia disintegration approach for dissolution analysis with that of the Food and Drug Administration's recommended rotating paddle technique for inducing aqueous disruption of the solid oral dosage form. RESULTS: The rationale and significance of the study focuses attention on the variation in release of the active ingredient observed relative to the four formulation strengths. With differences in the extent of dissolution noted and official standards in mind, emphasis is placed on the development of an alternate test protocol. CONCLUSIONS: Dissolution data derived via ultraviolet spectrophotometry revealed statistically significant differences in the amount of hydroxyzine hydrochloride being released from its coated structure, the extent of which was found to be dependent on the acid nature of the simulated gastric dissolution medium used and intensity of mixing action employed.

Effect of vehicle ionic strength on sorption of nitroglycerin to a polyvinyl chloride administration set.

The nitroglycerin sorptive properties of a polyvinyl chloride i.v. administration set were studied, and the role played by the admixture vehicle in this process was explored. Admixtures of nitroglycerin 0.4 mg/mL were prepared in sterile water for injection, 5% dextrose injection, Ringer's injection, and 0.25%, 0.9%, and 5% sodium chloride injection. Each admixture was divided into two 500-mL sterile glass containers, and flow through the administration set at 100 mL/hr was begun. Samples of effluent were collected at intervals beginning 10 minutes after the start of the infusion and ending at 180 minutes. Nitroglycerin depletion from solution and uptake by the set was determined by an ultraviolet spectrophotometric assay. Initially, the degree of nitroglycerin loss to the set was greatest for dextrose admixtures, intermediate for water admixtures, and least for sodium chloride admixtures. Losses of about 40% were observed during the first 10 minutes; between 15 and 20 minutes, the stated pattern of drug sorption was reversed, with sodium chloride admixtures now showing the greatest loss of nitroglycerin. The availability of nitroglycerin was an inverse function of increasing ionic strength during the three-hour observation period. Nitroglycerin availability in admixtures in contact with a polyvinyl chloride administration set was dependent on the ionic strength of the vehicle and the time points in the infusion period at which measurements were made.

Effect of procaine on the pH of buffered and unbuffered cardioplegic solutions.

Changes in pH values were studied in two types of cardioplegic admixtures containing procaine 0.95 meq/L: an institutional formulation based on Ringer's injection and buffered with tromethamine injection 3.6%, and Plegisol (Abbott Laboratories) buffered with sodium bicarbonate injection 8.4%. Initial pH was measured in the buffered and unbuffered solutions before the addition of procaine and after the addition of 13 mL of procaine hydrochloride injection 2% or 260 mg of procaine hydrochloride powder (reference standard). Buffered 1-L admixtures containing procaine hydrochloride injection were stored (the institutional formulations in glass and the Plegisol admixtures in flexible plastic bags) at 3-5 degrees C or 25 degrees C. Plegisol admixtures were prepared with 10 mL (10 meq or 840 mg) of buffer as directed by the manufacturer or with 3 mL (3 meq) of buffer. Admixture pH was tested after various time intervals. Of the unbuffered solutions containing procaine, pH values were lower in Plegisol than in the institutional formulation. Of the procaine-containing buffered Plegisol solutions, only the admixture containing 3.0 mL of buffer and procaine prepared from powder had an initial pH in the acceptable range of 7.30-7.60. In all the stored solutions, pH changed rapidly; solution pH changed less under refrigeration. In the stored institutional admixtures, pH was acceptable for 96 hours at 3-5 degrees C and 24 hours at 25 degrees C. In the stored Plegisol admixtures to which 10 mL of buffer was added, pH was greater than 7.6 initially and continued to increase.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, placebo-controlled trial of TRH in amyotrophic lateral sclerosis.

A double-blind, placebo-controlled trial of single doses of thyrotropin releasing hormone (TRH) was performed on 12 patients with amyotrophic lateral sclerosis. Each patient was given subcutaneous injections of TRH 150 mg or placebo, and IV infusions of TRH 500 mg or placebo at 72- to 96-hour intervals. Eight motor and functional ratings were scored at regular intervals after each injection. Side effects were seen in all patients and were obvious to patients and examiners, making true blinding impossible. Nevertheless, statistically significant improvement was seen only in dynametric strength 1 hour after subcutaneous injection (p less than 0.05). Significant improvement occurred, in one patient only, on subjective speech testing during IV infusion of TRH. In none of six other ratings was there a significant difference between TRH and placebo. Subjective improvement was noted by 11 of 12 patients.

Stability of procaine hydrochloride in a buffered cardioplegia formulation.

The stability of procaine hydrochloride in a buffered cardioplegia solution was studied. The formulation of Ringer's injection with added increments of potassium and magnesium plus procaine hydrochloride was buffered to a pH of 7.3-7.6 with tromethamine. Procaine hydrochloride content was measured in triplicate by ultraviolet spectrophotometry at set time intervals and at temperatures of 22, 40, and 61 degrees C. The time required for procaine to degrade to the lower shelf-life limit of 90% of its initial concentration was extrapolated to be approximately two days at room temperature and 11 days under refrigeration. It is recommended that the basic buffered cardioplegia solvent be manufactured separately, and the procaine hydrochloride be added at the time of dispensing to minimize its loss of potency.

Review of current knowledge of plastic intravenous fluid containers.

A review of the features of plastic intravenous fluid containers is presented. The following topics are discussed: (1) handling and storage; (2) environmental and human contamination; (3) particulate matter; (4) water vapor transmission; (5) drug additives; (6) leaching and adsorption; (7) possible toxicity; and (8) cost. It is concluded that various justifications can be presented for both glass and plastic containers.