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Results for “Drug Compounding”

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At least 19 recordsLinked to original sources
PubMed1978

A "carrier effect" observed in assay of antidiarrhoeal drug compounds.

A carrier effect has been shown to exist in a stable isotope dilution assay for diphenoxylate. When a tetradeuterated analogue is used as a carrier and internal standard a sevenfold increase in sensitivity is observed for the unlabelled compound. Examination of a related pharmacologically active compound (SC-27166) showed a much smaller effect.

Antidiarrheals↗
PubMed1978

Inhibition of collagen peptidase in HeLa cells and human tumours by compounds including drugs used in cancer therapy.

Collagen-peptidase activity in extracts of HeLa cells and human tumours is inactivated by Razoxane (ICRF-159), cyclophosphamide, 5-fluorouracil, thiotepa, aprotinin, EDTA and phenanthroline. As this activity, in association with other enzymes, may contribute to tissue lysis in cancers, chemical intervention may reduce invasiveness and modify the processes of infiltration and metastasis. Accordingly, some drugs used in therapy or for the prevention of metastasis may produce their observed effects by a combination of factors including enzyme inhibition.

Antineoplastic Agents↗
PubMed2026

Leveraging the genetics of psychiatric disorders to prioritize potential drug targets and compounds.

Genetics can inform biologically relevant drug development and repurposing, which may improve patient care. Here, we leverage the genetics of psychiatric disorders to prioritize potential drug targets and compounds. We used the genome-wide association studies of four psychiatric disorders [attention deficit hyperactivity disorder (ADHD), bipolar disorder, depression, and schizophrenia] and genes encoding drug targets. We conducted drug enrichment analyses incorporating the novel and biologically specific GSA-MiXeR tool. We conducted multiple molecular trait analyses using large-scale transcriptomic and proteomic datasets sampled from brain and blood tissue. This included the novel use of the UK Biobank proteomic data for a proteome-wide association study of psychiatric disorders. With the accumulated evidence, we prioritize potential drug targets and compounds for each disorder. We reveal candidate drug targets associated with a single or multiple disorders that implicate glutamate signaling. Drug prioritization indicated genetic support for psychotropic medications, including several top-ranked antipsychotics for schizophrenia. We also observed genetic support for commonly used psychotropics for psychiatric treatment (e.g., clozapine, duloxetine, and lithium). Revealed opportunities for drug repurposing included cholinergic drugs for ADHD, estrogen modulators for depression, and matrix metalloproteinases for ADHD and depression. Our findings indicate the genetic liability to schizophrenia is associated with reduced brain and blood expression of CYP2D6, a gene encoding a metabolizer of drugs and neurotransmitters, suggesting a genetic risk for poor drug response and altered neurotransmission. Our extensive analyses highlight the utility of genetics for informing drug development and repurposing for psychiatric disorders, providing novel opportunities for improving patient outcomes. Depicted is the series of analyses conducted to generate a list of prioritized drug targets and compounds. First pairings of genome-wide association study (GWAS) traits with drugs are generated using enrichment analyses. Next, a series of molecular trait analyses is conducted to generate and rank a list of potential drug targets for each GWAS trait. Finally, enrichment and molecular trait results are combined to generate a ranked list of prioritized drugs for each GWAS trait based on supporting genetic evidence. ADHD = Attention deficit hyperactivity disorder, BIP = Bipolar disorder, DEP = Depression, SCZ = Schizophrenia, DBP = Diastolic blood pressure, T2D = Type 2 diabetes, RNA = ribonucleic acid, XWAS = both transcriptome and proteome-wide association studies, MR = Mendelian randomization, coloc = colocalization.

Humans↗
PubMed1978

Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride.

Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vitro assays. This initial report describes the results for one of these compounds, Naltrexone. Nalrexone is a relatively nontoxic drug antagonist related to Naloxone which appears to be effective in diminishing the euphoria and dependence upon heroin in clinical studies. With the exception of weak nonspecific DNA damage observed in an E. coli DNA repair test and possibly with WI-38 cells as well, Naltrexone did not demonstrate significant potential for the induction of gene mutations or chromosomal aberrations under the conditions of this evaluation.

Animals↗
PubMed1977

Different proliferative responsiveness of fibroblasts and mesothelial cells in the rat mesentery following administration of compound 48/80 at various hours of the day.

The proliferative responsiveness of fibrolasts and mesothelial cells in the mesenterial membrane of normal rats was studied quantitatively after a single i.p. injection of the mast-cell activating and histamine-releasing drug Compound 48/80. To make some allowance for a possible chronobiologic effect of the circadian type on the induced proliferation, the drug was given at 1 a.m., 9 a.m., or 5 p.m., and the animals were examined 16, 24, and 32 h later. The proliferation was estimated by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei, and by mitotic frequency counting. The main result was that a larger fraction of fibroblasts than of mesothelial cells was stimulated to proliferation, regardless of the hour of treatment with Compound 48/80. It was further demonstrated that in control animals the fraction of cells of either fibroblastic or mesothelial type present in the S cum G2 cell-cycle phases varied markedly at different hours of the day. Quantitative differences appeared in the induced proliferation with regard to the hour of treatment. The most vigorous proliferative response appeared after administration of the drug at 9 a.m. The fraction of cells in the S cum G2 cell-cycle phases was then increased at 16 h and the fraction of dividing cells at 24 h after treatment, illustrating the promptness of the induced proliferative reaction.

Animals↗
PubMed1975

Stabilizing effect of inorganic phosphate salts on antibiotic-steroid ophthalmic preparations.

Drocinonide phosphate potassium forms an insoluble complex with neomycin sulfate in aqueous solution. Dibasic sodium phosphate can be employed in an ophthalmic formulation to prevent the formation of this precipitate without affecting the stability of the steroid or the bioactivity of the antibiotic. Other phosphate steroid salts behaved in a like manner.

Chemistry, Pharmaceutical↗
PubMed1976

Implant pellets I: effects of compression pressure on in vivo dissolution of delmadinone acetate pellets.

A formulation containing 95% delmadinone acetate was compressed at three different pressures. These pressures resulted in a pellet density difference of 19%. In vivo dissolution profiles were determined for five lots of pellets. The pellets were implanted subcutaneously in rats, removed periodically, and assayed chemically for remaining steroid. The resulting data were fit, using the computer program NONLIN, to a dissolution model. The dissolution rate for the lot with the lowest density made at the lowest compression was statistically (p less than 0.05) different from the four other lots. A possible explanation for this increased dissolution rate could be that channeling occurs within the pellet, thereby increasing the effective dissolving surface. The results also indicate that equivalent dissolution rates between lots are reached at a certain compression and density.

Animals↗
PubMed1976

Development of a stable sublingual nitroglycerin tablet II: formulation and evaluation of tablets containing povidone.

Stable and pharmaceutically elegant sublingual nitroglycerin tablets were formulated using povidone to retard volatilization of the drug. Formulation and processing variables were investigated to produce an acceptable product. A blend of two grades of povidone, of different degrees of cross-linkage and water solubility, provided stable tablets which exhibited rapid disintegration. Directly compressed sublingual tablets made in this study retained over 80% of the initial nitroglycerin when exposed to the atmosphere at room temperature for 2 months. The direct compression tablets are of good appearance and low friability, and the formulation is readily compressed without problems. An interesting relationship among the hardness, disintegration time, and compaction pressure is described.

Drug Compounding↗
PubMed1976

In vitro and in vivo availability of spironolactone from oral dosage forms.

Tablet formulations of spironolactone with hydrochlorothiazide were studied in vitro and in vivo to evaluate the effect of formulation parameters on the bioavailability of spironolactone. The time required for 50% tablet dissolution (T50) in simulated gastric fluid was linearly correlated with the disintegration times of four experimental formulations and one commercial tablet of spironolactone and hydrochlorothiazide. Bioavailability studies were conducted in four healthy, female beagle dogs. The mean time to peak concentration of canrenone,f cancrenone, the major metabolite of spironolactone, was proportional to the T50 dissolution parameter. A study of spironolactone administered orally with and without hydrochlorothiazide showed that the bioavailability of spironolactone is not affected by hydrochlorothiazide. No significant difference in the bioavailability of spironolactone from one 100-mg and four 25-mg tablets were observed. Estimates of some pharmacokinetic parameters for canrenone closely agreed with those previously reported.

Animals↗
PubMed1977

Application of gluconolactone in direct tablet compression.

Gluconolactone was evaluated as an excipient for tablets prepared by direct compression using various drugs known to be difficult to compress. The physical properties of the tablets were evaluated after compression and after storage and were satisfactory. Comparative studies were conducted between gluconolactone and anhydrous lactose, a common direct compression diluent, for development of static charges during blending, flow, drug distribution, drug stratification, color distribution, compressibility, and preservation against mold growth. Gluconolactone possesses those properties necessary to produce high quality tablets by the direct compression process. Separate powdered mixtures of aspirin USP with gluconolactone, anhydrous lactose, spray-dried lactose, mannitol, and sorbitol were stored at various humidities and temperatures for specified periods and tested for the integrity of aspirin. Gluconolactone contributed least to the degradation of the drug as compared to other excipients studied. A preliminary in vivo study also was conducted on the bioavailability of aspirin from separate and similar mixtures with gluconolactone, anhydrous lactose, and starch. Gluconolactone did not show any inhibitory effect on aspirin absorption.

Animals↗
PubMed1977

Determination of porosity and pore-size distribution of aspirin tablets relevant to drug stability.

Total porosity and pore-size distribution of aspirin tablets prepared from aspirin, starch USP, and precipitated colloidal silicon dioxide were determined using mercury porosimetry. The model represented a hydrolyzable drug substance in combination with simple excipients. The role of starch and silicon dioxide on the microstructure of the tablets was investigated, as was the chemical stability of various systems. In general, the porosity of tablets containing a constant quantity of starch increased linearly with silicon dioxide concentration. Examination of the pore-size distribution, however, revealed that a low concentrations silicon dioxide functioned primarily to reduce the size and volume of coarse pores representing the spaces between the agglomerates of starch and aspirin particles. This effect was optimum at 3%. A further increase in silicon dioxide concentration produced tablets with relatively larger pore sizes. Studies of changes in the porosity characteristics of tablets as influenced by water vapor over time showed distinct differences in this complex parameter. A unique trend in the change of the pore-size distribution was noted with tablets containing 3% silicon dioxide. These observations are discussed relative to the stability of aspirin tablets in which this concentration of silicon dioxide produced a maximum stabilizing effect.

Aspirin↗