Investigations of Some Physicochemical Properties of Haloperidol Which May Affect Its Activity

The genetic basis of most heritable traits is complex. Inhibitory compounds and their effects in model organisms have been used in many studies to gain insights into the genetic architecture underlying quantitative traits. However, the differential effect of compound concentration has not been studied in detail. In this study, we used a large segregant panel from a cross between two genetically divergent yeast strains, BY4724 (a laboratory strain) and RM11_1a (a vineyard strain), to study the genetic basis of variation in response to different doses of a drug. Linkage analysis revealed that the genetic architecture of resistance to the small-molecule therapeutic drug haloperidol is highly dose-dependent. Some of the loci identified had effects only at low doses of haloperidol, while other loci had effects primarily at higher concentrations of the drug. We show that a major QTL affecting resistance across all concentrations of haloperidol is caused by polymorphisms in SWH1, a homologue of human oxysterol binding protein. We identify a complex set of interactions among the alleles of the genes SWH1, MKT1, and IRA2 that are most pronounced at a haloperidol dose of 200 µM and are only observed when the remainder of the genome is of the RM background. Our results provide further insight into the genetic basis of drug resistance.

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“…1A ). Acidic pH ( = 4.3) [26] completely rescued growth in the presence of 150 µM haloperidol ( Fig. 1A ).…”

Section: Resultsmentioning

confidence: 91%

Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

Wang

Kruglyak

2014

PLoS Genet

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“…Lactic acid (1%) was added to the formulation to enable the drug to dissolve. HAL is known to be stable in aqueous lactic acid solutions at room temperature [32] and known to be a saliva stimulant, which is of relevance when formulating an orodispersible drug formulation [33]. Erythrosine was chosen as colorant due to its good solubility in ethanol and glycerol was added as a plasticizer.…”

Section: Ink Formulation Developmentmentioning

confidence: 99%

Stencil Printing—A Novel Manufacturing Platform for Orodispersible Discs

et al. 2020

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Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6–17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 µm thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals.

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Compatibility of haloperidol and hyoscine-N-butyl bromide in mixtures for subcutaneous infusion to cancer patients in palliative care

Barcia

Reyes

Azuara

et al. 2003

Support Care Cancer

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The administration of drugs by s.c. infusion is routinely practiced in palliative medicine for the management of patients who are no longer able to take oral medication. It is not uncommon for two or more drugs to be combined in s.c. infusion solutions. Unfortunately, the compatibility and stability of haloperidol and hyoscine-N-butyl bromide has not yet been determined. The objective of this study was to study the compatibility and stability of solutions containing both drugs in polypropylene syringes. Nine different solutions were assessed for up to 15 days following preparation. The solutions were prepared in polypropylene syringes with 0.9% saline as a diluent and stored at 4°C and 25°C. High-performance liquid chromatography was the analytical technique used to measure haloperidol and hyoscine-N-butyl bromide. The initial concentration ranges were 0.3125-1.25 mg/ml for haloperidol and 2.5-10.0 mg/ml for hyoscine-Nbutyl bromide. Haloperidol was pre-cipitated at a concentration of ≥1.25 mg/ml when it was combined with hyoscine-N-butyl bromide. Concentrations of hyoscine-N-butyl bromide lower than 10 mg/ml in mixtures with haloperidol or 0.625 mg/ml of haloperidol in mixtures with hyoscine-N-butyl bromide for s.c. infusion allow for the administration of both drugs without any significant loss after storage at 25°C for periods of up to 15 days, with approximately ≥90% and 88%, respectively, of haloperidol and hyoscine-N-butyl bromide remaining. However, after storage of the mixtures for equivalent periods at 4°C the losses of hyoscine-N-butyl bromide observed at the end of the study were higher than 20%, while the percentages of haloperidol remaining after 15 days at this temperature were ≥94.37%.

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Investigations of Some Physicochemical Properties of Haloperidol Which May Affect Its Activity

Cited by 13 publications

References 7 publications

Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

Genetic Basis of Haloperidol Resistance in Saccharomyces cerevisiae Is Complex and Dose Dependent

Stencil Printing—A Novel Manufacturing Platform for Orodispersible Discs

Compatibility of haloperidol and hyoscine-N-butyl bromide in mixtures for subcutaneous infusion to cancer patients in palliative care

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