Seminar LN

School of Health and Allied Sciences

Pokhara University

1

The comparative pharmacokinetics study of Ginseng fruit, Ginkgo biloba plant and drug Isoniazid inhalation powder by a proliposome delivery

system.Laxmi N. Neupane

Seven Semester, B. Pharm.School of Health and Allied Sciences

Pokhara University, Lekhanath-12, Kaski Nepal

05/01/2023 Pharmaceutical Seminar 5


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Contents

IntroductionMaterial and MethodsResults and DiscussionConclusionReferences

05/01/2023 Pharmaceutical Seminar 5 2


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Introduction

Liposome are the most promising and broadly applicable of all the novel delivery systems.

Need for development of proliposome: Stability Proliposome are dry, free-flowing granular products

composed of drug and phospholipids which upon addition of water, disperse to form a multi-lamellar liposomal suspension.



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Contd…

Ginseng Fruit Saponins (GFS) Chinese herbal medicine, highly used Saponins extracted: berry of ginseng possess higher ginsenoside for treating many disease.

Improvement bioavailability of GFS Phospholipids have the characteristics of excellent

biocompatibility and amphiphilicity, thus employed as important pharmaceutical excipients.



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Contd…

Ginkgo biloba extract (GbE) living fossil tree Used medicinally for many centuries, benefits of GbE are

presumed to result from the synergistic effect of two distinct groups of compounds: flavonoids and terpenoid.

Why Improvement oral bioavailabilities? The flavonoids are relatively low due to their poor solubility. Therefore, an oral proliposome formulation loaded with GbE

(GbP) was developed to enhance the absorption of ginkgo flavonoids.



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Cont…

Isoniazid (INH) First-line hydrophilic antituberculosis agent Difficult to encapsulate in liposomes: Liposomes in

aqueous systems suffer from physical instability. Other potential liposome instabilities are sedimentation,

and aggregation or fusion of the liposomes during storage. Overcome this problem Isoniazid proliposome powders for

inhalation is required.



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Material and Methods

1. Chemicals, reagents and animalsFor Ginseng fruit Ethyl acetate, acetonitrile,

methanol, ethyl acetate, isopropanol and phosphoric acid

Sodium deoxycholate, mannitol, anhydrous ethanol, hydrochloric acid, and other reagents of analytical grade

For Ginko biloba extract Ethyl acetate, acetonitrile

and formic acid tablet with 40 mg of

G.biloba extract standardized composition of

9.6 mg of flavonoids and 2.4 mg of terpene lactone



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Contd…For Ginseng fruit2. Preparation of P-GFS3. Optimization of

proliposomes4. HPLC analysis of

ginsenoside Re5. Assay and determination

of entrapment efficiency6. Measurement of particle

size and zeta potential of the reconstituted liposome

For Ginko biloba extract2. Chromatographic and

mass spectrometry conditions

3. Preparation of standards and quality control samples

4. Preparation of plasma samples



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Contd…

For Ginseng fruit7. Solid state

characterization Field emission-scanning

electron microscope (FE-SEM) Differential scanning

colorimetry (DSC) Fourier transform infrared (FT-

IR) spectroscopy

For Ginko biloba extract5. Method validation Specificity and selectivity Sensitivity and linearity Accuracy and precision Matrix effect and extraction

recovery Dilution integrity Pharmacokinetic study Statistical analysis



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Contd…For Ginseng fruit8. In vitro release study9. Oral bioavailability study Animals ( Wistar rat) Pharmacokinetic study Assay method• UPLC-MS/MS analysis of ginsenoside Re in plasma. A Waters Acquity

UPLC system• Sample preparation.

10. Data analysis11. Stability studies



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Contd…


Preparation of proliposome by spray drying method


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Results and Discussion

1. Pharmacokinetics study Time of the maximum concentration (Tmax) The maximum plasma concentration (Cmax) The elimination half-time (T1/2) The area under concentration–time curve (AUC0-t) The plasma clearance (CL)



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Contd…



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Contd… 2. Measurement of particle size and zeta potential of the

reconstituted liposomes

Liposomes showed a size range of 275.4 ±10.74 nm The zeta potential value was 28.6 ±4.77 mV



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Contd…


Size distribution (A) and (B) zeta potential distribution of the reconstituted liposomes


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Contd…

3. Solid state charaterization Field emission-scanning electron microscope (FE-SEM):

The surface morphology of mannitol, GFS and reconstituted liposomes were investigated by FE-SEM. The reconstituted solution prepared by adding distilled water into the powder of mannitol, GFS and P-GFS were all dried naturally on the silicon wafer.

Differential scanning colorimetry (DSC): the molecular state of mannitol is evaluated.



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Contd…

4. Mass spectrophotometry UPLC-MS/MS : determination of compounds in biological

samples with improve sensitivity, selectivity and specificity.

The key parameter: capillary voltage, source voltage, source temperature, desolvation temperature, cone gas flow, desolvation gas flow, cone voltage and collision energy were carefully optimized in both positive and negative electrospray ionization modes.



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Contd…5. Chromatography Chromatographic conditions were further optimized to

produce the best sensitivity, efficiency and chromatographic peak shape.



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Contd…6. Aerosol Performance of Proliposome Powder INH-particles deposited on glass device, glass throat and

preseparator, thus overcome the problem mass median aerodynamic diameter (MMAD) should be less than 5 µm in order to reach the lower part of the respiratory tract.

Fine particle fraction and MMAD will also depends on the inhaler device.

Microporous particles: more lipid content and high void space, and may improve aerosol perfomance.


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Conclusion In this study, a drug delivery system of proliposome was

prepared with optimum conditions for oral administration by the spray drying method.

the results showing that the proliposome formulation had a significant effect on absorption, elimination and bioavailability of G. biloba flavonoids and terpenoid lactones in comparison with the ordinary tablet.

INH-proliposome exhibited better antimycobacterial activity against M. bovis-infected AM than did free INH.



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References Hao F, He Y, Sun Y, Zheng B, Liu Y, Wang X, Zhang Y, Lee RJ, Teng L, Xie J (2016),

Improvement of oral availability of ginseng fruit saponin by a proliposome delivery system containing sodium deoxycholate, Saudi Journal of Biological Sciences, 23, 113-125.

Zheng B, Xing G, Bi Y, Yan G, Wang J, Cheng Y, Liu Y, Ashraf M A, Xie J, (2016), Comparative pharmacokinetics of a proliposome formulation of Ginkgo biloba extract and Ginaton in rats by a sensitive ultra-performance liquid chromatography-tendem mass spectrometry method, Biological Sciences, 23, 54-65

Rojanarat W, Changsan N, Tawithong E, Pinsuwan S, Chan H K, Srichana T, (2011), Isoniazid Proliposome Powders for Inhalation- Preparation, Characterization and cell structure studies, International Journal of Molecular Sciences, 12, 4414-4434



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