Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu.

Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu.

Pharmaceutical development and technology (2013-11-14)

Srinivasa M Sammeta, Li Wang, Shravan K Mutyam, Kathleen O'Loughlin, Carol E Green, Milton H Werner, Terence Kelly, Gita N Shankar

PMID24218989

ABSTRACT

The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-β-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague-Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar.

MATERIALS

Product Number

Brand

Product Description

S0876

Sigma-Aldrich

Sodium phosphate dibasic, ReagentPlus^®, ≥99.0%

S5136

Sigma-Aldrich

Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%

S7907

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Sodium phosphate dibasic, BioXtra, ≥99.0%

B7901

Sigma-Aldrich

Boric acid, suitable for electrophoresis, ≥99.5%

B7660

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Boric acid, BioXtra, ≥99.5%

B2645

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Boric acid, tablet, 1 g boric acid per tablet

S3264

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Sodium phosphate dibasic, for molecular biology, ≥98.5% (titration)

82280

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1,2-Propanediol, puriss. p.a., ACS reagent, ≥99.5% (GC)

71636

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Sodium phosphate dibasic, BioUltra, for molecular biology, ≥99.5% (T)

82281

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1,2-Propanediol, tested according to Ph. Eur.

G2289

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Glycerin, meets USP testing specifications

G9012

Sigma-Aldrich

Glycerol, ≥99.5%

G2025

Sigma-Aldrich

Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)

G5516

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Glycerol, for molecular biology, ≥99.0%

G6279

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Glycerol, BioXtra, ≥99% (GC)

71642

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Sodium phosphate dibasic, purum p.a., anhydrous, ≥98.0% (T)

202878

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Boric acid, 99.999% trace metals basis

339067

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Boric acid, 99.97% trace metals basis

16033

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1,2-Propanediol, meets analytical specification of Ph. Eur., BP, USP, ≥99.5%

15663

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Boric acid, BioUltra, for molecular biology, ≥99.5% (T)

49767

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Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)

258024

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α-Tocopherol, ≥95.5%

398039

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1,2-Propanediol, ACS reagent, ≥99.5%

255793

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Sodium phosphate dibasic, 99.95% trace metals basis

W252506

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Glycerol, FCC, FG

RDD038

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Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%, free-flowing, Redi-Dri^™

77067

Supelco

Glycerol, analytical standard

49770

Sigma-Aldrich

Glycerol, puriss. p.a., ACS reagent, anhydrous, dist., ≥99.5% (GC)

71640

Sigma-Aldrich

Sodium phosphate dibasic, puriss. p.a., ACS reagent, anhydrous, ≥99.0% (T)

11607

Sigma-Aldrich

Boric acid, puriss., meets analytical specification of Ph. Eur., BP, NF, 99.5-100.5%, powder