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  • 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
Y0001547
Propylene glycol, European Pharmacopoeia (EP) Reference Standard
PHR1329
Supelco
Potassium Chloride, Pharmaceutical Secondary Standard; Certified Reference Material
77067
Supelco
Glycerol, analytical standard
P3911
Sigma-Aldrich
Potassium chloride, ACS reagent, 99.0-100.5%
S8263
Sigma-Aldrich
Sodium hydroxide solution, 5.0 M
15523
Sigma-Aldrich
Glycerol, puriss., anhydrous, 99.0-101.0% (alkalimetric)
15524
Sigma-Aldrich
Glycerol solution, puriss., meets analytical specification of Ph. Eur., BP, 84-88%
05211
Sigma-Aldrich
Sodium hydroxide solution, purum, ≥32%
60130
Sigma-Aldrich
Potassium chloride, puriss. p.a., ≥99.5% (AT)
746436
Sigma-Aldrich
Potassium chloride, anhydrous, free-flowing, Redi-Dri™, ACS reagent, ≥99%
P4504
Sigma-Aldrich
Potassium chloride, ReagentPlus®, ≥99.0%
G7757
Sigma-Aldrich
Glycerol, ReagentPlus®, ≥99.0% (GC)
G7893
Sigma-Aldrich
Glycerol, ACS reagent, ≥99.5%
S9763
Sigma-Aldrich
Sodium phosphate dibasic, ACS reagent, ≥99.0%
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
31146
Sigma-Aldrich
Boric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., buffer substance, ≥99.8%
B0252
Sigma-Aldrich
Boric acid, ReagentPlus®, ≥99.5%
1576708
USP
Propylene glycol, United States Pharmacopeia (USP) Reference Standard
V900068
Sigma-Aldrich
Potassium chloride, Vetec™, reagent grade, 99%
1295607
USP
Glycerin, United States Pharmacopeia (USP) Reference Standard
04276
Sigma-Aldrich
Sodium phosphate dibasic, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E 339, anhydrous, 98-100.5% (calc. to the dried substance)
793590
Sigma-Aldrich
Potassium chloride, anhydrous, free-flowing, Redi-Dri™, ReagentPlus®, ≥99%
12636
Sigma-Aldrich
Potassium chloride, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E508, 99-100.5% (AT), ≤0.0001% Al
415413
Sigma-Aldrich
Sodium hydroxide solution, 50% in H2O
49770
Sigma-Aldrich
Glycerol, puriss. p.a., ACS reagent, anhydrous, dist., ≥99.5% (GC)
RDD038
Sigma-Aldrich
Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%, free-flowing, Redi-Dri™
T1539
Sigma-Aldrich
(+)-α-Tocopherol, Type VI, from vegetable oil, liquid (≥0.88M based on potency, density and molecular wt.), BioReagent, suitable for insect cell culture, ≥1000 IU/g
S0876
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Sodium phosphate dibasic, ReagentPlus®, ≥99.0%
S5136
Sigma-Aldrich
Sodium phosphate dibasic, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%