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  • Conversion of solid dispersion prepared by acid-base interaction into free-flowing and tabletable powder by using Neusilin® US2.

Conversion of solid dispersion prepared by acid-base interaction into free-flowing and tabletable powder by using Neusilin® US2.

International journal of pharmaceutics (2015-03-01)
Ankita Shah, Abu T M Serajuddin
ABSTRACT

A novel method of greatly increasing solubility and dissolution rate of a model basic drug, haloperidol, by interacting it with water-soluble weak organic acids in aqueous media was previously reported in the literature. Amorphous solid dispersion (SD) was formed when solutions containing haloperidol and various acids were dried. However, the SDs were semisolid, viscous and sticky, especially when the drug load was high, and could not be processed into tablets. The drug release from SD was also incomplete since the viscous material did not readily mix with aqueous media. In the present study, a mesoporous metalosilicate, Neusilin(®) US2, was incorporated in SDs prepared by using malic, tartaric and citric acids. The silicate constituted 40% w/w of the total solid mass. The addition of silicate converted SDs into powders, which were then characterized for flow properties, bulk and tap density, and tabletability. Their physical properties were found to be acceptable for the development of tablets. DSC and powder XRD showed that haloperidol and acids converted completely to amorphous forms, and they did not show any sign of crystallization during accelerated stability study at 40°C/75% RH and 25°C/60% RH for 9 months. Complete drug release under gastrointestinal pH conditions could be obtained from tablets prepared.

MATERIALS
Product Number
Brand
Product Description

Haloperidol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Magnesium stearate, puriss., meets analytical specification of Ph. Eur., BP, ≥90% stearic and palmitic acid basis, ≥40% stearic acid basis (GC), 4.0-5.0% Mg basis (calc on dry sub.)
Sigma-Aldrich
Haloperidol, powder
Sigma-Aldrich
Magnesium stearate, technical grade
USP
Haloperidol, United States Pharmacopeia (USP) Reference Standard
Haloperidol for peak identification, European Pharmacopoeia (EP) Reference Standard
Haloperidol for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Citric acid, ≥99.5%, FCC, FG
Sigma-Aldrich
DL-Malic acid, ReagentPlus®, ≥99%
Sigma-Aldrich
DL-Malic acid, meets analytical specification of FCC, E296, 99-100.5% (alkalimetric)
Sigma-Aldrich
Citric acid, BioUltra, anhydrous, ≥99.5% (T)
Sigma-Aldrich
2-Hydroxybutyric acid sodium salt, 97%
Sigma-Aldrich
Citric acid, ACS reagent, ≥99.5%
Sigma-Aldrich
DL-Malic acid, ≥98% (capillary GC)
Sigma-Aldrich
Malic acid, meets USP/NF testing specifications
Sigma-Aldrich
Citric acid, anhydrous, suitable for cell culture, suitable for plant cell culture
Sigma-Aldrich
Citric acid, 99%
Supelco
Citric acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
USP
Citric acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
DL-Malic acid, 99%
Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard
Supelco
DL-Malic acid, analytical standard
Supelco
Malic acid, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Malic acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Tartaric Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Sigma-Aldrich
Citric acid, meets analytical specification of Ph. Eur., BP, USP, E330, anhydrous, 99.5-100.5% (based on anhydrous substance)