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

ZUSAMMENFASSUNG

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.

MATERIALIEN

Produktnummer

Marke

Produktbeschreibung

P3911

Sigma-Aldrich

Kaliumchlorid, ACS reagent, 99.0-100.5%

G7893

Sigma-Aldrich

Glycerin, ACS reagent, ≥99.5%

221465

Sigma-Aldrich

Natriumhydroxid, ACS reagent, ≥97.0%, pellets

G5516

Sigma-Aldrich

Glycerin, for molecular biology, ≥99.0%

S5881

Sigma-Aldrich

Natriumhydroxid, reagent grade, ≥98%, pellets (anhydrous)

S9763

Sigma-Aldrich

Natriumphosphat, ACS reagent, ≥99.0%

G7757

Sigma-Aldrich

Glycerin, ReagentPlus^®, ≥99.0% (GC)

415413

Sigma-Aldrich

Natronlauge, 50% in H₂O

B0394

Sigma-Aldrich

Borsäure, ACS reagent, ≥99.5%

72068

Sigma-Aldrich

Natronlauge, BioUltra, for molecular biology, 10 M in H₂O

71640

Sigma-Aldrich

Natriumphosphat, puriss. p.a., ACS reagent, anhydrous, ≥99.0% (T)

S8045

Sigma-Aldrich

Natriumhydroxid, BioXtra, ≥98% (acidimetric), pellets (anhydrous)

12636

Sigma-Aldrich

Kaliumchlorid, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E508, 99-100.5% (AT), ≤0.0001% Al

P9541

Sigma-Aldrich

Kaliumchlorid, for molecular biology, ≥99.0%

S2770

Sigma-Aldrich

Natronlauge, 1.0 N, BioReagent, suitable for cell culture

06203

Sigma-Aldrich

Natriumhydroxid, puriss., meets analytical specification of Ph. Eur., BP, NF, E524, 98-100.5%, pellets

655104

Sigma-Aldrich

Natriumhydroxid, reagent grade, 97%, powder

P5405

Sigma-Aldrich

Kaliumchlorid, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%

306576

Sigma-Aldrich

Natriumhydroxid, pellets, semiconductor grade, 99.99% trace metals basis

B0252

Sigma-Aldrich

Borsäure, ReagentPlus^®, ≥99.5%

B6768

Sigma-Aldrich

Borsäure, BioReagent, for molecular biology, suitable for cell culture, suitable for plant cell culture, ≥99.5%

W294004

Sigma-Aldrich

Propylenglycol, ≥99.5% (GC), FCC, FG

P4504

Sigma-Aldrich

Kaliumchlorid, ReagentPlus^®, ≥99.0%

T3251

Sigma-Aldrich

(±)-α-Tocopherol, synthetic, ≥96% (HPLC)

04276

Sigma-Aldrich

Natriumphosphat, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E 339, anhydrous, 98-100.5% (calc. to the dried substance)

49781

Sigma-Aldrich

Glycerin -Lösung, 83.5-89.5% (T)

S8263

Sigma-Aldrich

Natronlauge, 5.0 M

60142

Sigma-Aldrich

Kaliumchlorid -Lösung, BioUltra, for molecular biology, ~1 M in H₂O

31146

Sigma-Aldrich

Borsäure, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., buffer substance, ≥99.8%

G2025

Sigma-Aldrich

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