ABSTRACT
Objective: To establish an HPLC method for the separation of optical isomers of palonosetron hydrochloride by RP-HPLC with HP-β-cyclodextrin ( HP-β-CD) as the chiral additive. Methods:The optimal separation process was performed on a Shi-seido CAPACELL PAK C18 VG 120 (250 mm × 4. 6 mm,5μm) column,the mobile phase was triethylamine (TEA) with HP-β-CD at different concentrations, the pH value was adjusted by acetic acid, the detection wavelength was 240nm, and the column temperature was 30℃. Results:The mobile phase was 0. 5% TEA (1% HP-β-CD, adjusting pH to 5. 5 with acetic acid)-acetonotirile (85∶15);the detection wavelength was 240nm, and the flow rate was 0. 5 ml·min-1 . The S, R-Isomer of palonosetron hydrochloride could be well separated. Conclusion:The method can be used as the optical isomer quality control for palonosetron hydrochloride.
ABSTRACT
Etoricoxib, a widely prescribed anti-inflammatory drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for increasing its oral bioavailability. The objective of the study is to evaluate the feasibility of formulating etoricoxib – CD (βCD/ HPβCD) – Poloxamer 407 and etoricoxib – CD (βCD/ HPβCD) –PVP K30 inclusion complexes into tablets and to evaluate the effects of CDs, Poloxamer 407 and PVP K30 on the dissolution rate of etoricoxib tablets. A comparative evaluation of wet granulation and direct compression methods was made for the preparation of tablets employing drug – CD –Poloxamer 407 / PVP K30 inclusion complexes. Drug – CD- Poloxamer 407 / PVP K30 inclusion complexes were prepared by kneading method. Tablets each containing 60 mg of etoricoxib were prepared by wet granulation and direct compression methods employing various CD complexes and the tablets were evaluated for dissolution rate and other physical properties. toricoxib tablets made by direct compression method disintegrated rapidly when compared to those made by wet granulation method. Tablets formulated employing βCD complexes disintegrated relatively more rapidly than those formulated employing HPβCD complexes. Etoricoxib dissolution was rapid and higher from the tablets formulated employing drug- CD- Poloxamer 407/ PVP K30 inclusion complexes when compared to the tablets containing etoricoxib alone and drug – CD complexes in both wet granulation and direct compression methods. In both the methods tablets formulated employing βCD complexes gave higher dissolution rates (K1) and DE30 values when compared to those formulated employing HPβCD complexes. Tablets formulated employing dug – βCD – Poloxamer 407 and drug – βCD – PVP K30 complexes and prepared by direct compression method gave higher dissolution rates, 0.0539 and 0.0459 min-1 respectively when compared to plain tablets (0.0124 min-1 ) as well as tablets containing drug – βCD complexes (0.0417 min-1). Hence a combination of βCD with Poloxamer 407 or PVP K30 is recommended to enhance the dissolution rate of etoricoxib tablets.