Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster T max (27 ± 5 min) with higher C max (1236 ± 116 ng/mL) and AUC (0-12) (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.
Two chromatographic methods were developed for simultaneous determination of some drugs used in common cold. First method is TLC-Densitometric method for the simultaneous estimation of Ambroxol hydrochloride (AMB), Pseudoephedrine hydrochloride (PSE) and Desloratadine (DES) in pure form and in pharmaceutical dosage form, the best resolution was obtained by the use of mobile phase (Ethyl acetate: methanol: ammonia), (14: 0.8: 0.5, v/v/v), the scanning of spots was performed at 254 nm in concentration range (1-40 ug/spot), (5-35 ug/spot),(0.2-2) ug/spot for AMB, PSE and DES, respectively. With LOD 0.262, 0.358 and 0.006 ug/ml. And LOQ 0.793, 1.09 and 0.018 ug /ml for AMB, PSE and DES, respectively. Second method is HPLC-UV Method for the Simultaneous determination of Ambroxol hydrochloride(AMB),Pseudoephedrine hydrochloride(PSE), Desloratadine (DES) and levoceterizine dihydrochloride (LVC) in quaternary mixture by using mobile phase consisted of acetonitrile: 0.01 M phosphate buffer (PH 5.5) (50:50, v/v) in an isocratic mode through inertsil C8 (250mm x 4.6mm, 5 µ) column at a flow rate of 1.3 ml/min. UV detection was carried out at 215 nm in concentration range (1.6-40), (3.2-40) , (0.6-9), (2.4-8.4 ) ug/ml for AMB, PSE , DES and LVC, respectively .With LOD 0.428, 0.180, 0.125 and 0.124, ug/ml And LOQ 1.299 , 0.550, 0.379, and 0.375ug/ml for AMB, PSE , DES and LVC, respectively The validation of the proposed methods was done according to ICH guidelines.
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