كلية الصيدلة.

Faculty of Pharmacy.

A Thesis For The Partial fulfillment of the Master Degree in Pharmaceutical Sciences “PHARMACEUTICS”.

Includes Bibliographic Referances, p208:226.

Abstract
Vinpocetine is a CNS acting drug, it is used for treatment of many
diseases like depression, Alzheimer and many cerebrovascular diseases.
Vinpocetine has limited oral use due to its low water solubility, slow dissolution
rate, poor absorption and significant first-pass metabolism that led to very low
bioavailability. Additionally, it has very rapid elimination rate with short halflife
that results in frequent drug dosing (three times daily), that increases side effects, toxicity and decreases patient compliance.
The objective of this study was to enhance the bioavailability of Vinpocetine by developing new nanostructured formulae. Abstract
Vinpocetine is a CNS acting drug, it is used for treatment of many
diseases like depression, Alzheimer and many cerebrovascular diseases.
Vinpocetine has limited oral use due to its low water solubility, slow dissolution
rate, poor absorption and significant first-pass metabolism that led to very low
bioavailability. Additionally, it has very rapid elimination rate with short halflife
that results in frequent drug dosing (three times daily), that increases side
effects, toxicity and decreases patient compliance.
The objective of this study was to enhance the bioavailability of Vinpocetine by developing new nanostructured formulae.
The systems were prepared and characterized by testing their pH,
entrapment efficiency (E.E), particle size (P.S), polydispersity index (PDI) and
zeta potential (Z.P). Particle size values of all systems were less than 320 nm
with relatively low polydispersity index and suitable zeta potential values
indicating the validity of the utilized ingredients and the modified preparation
technique to produce micellar nanodispersions.
Desirability values were calculated to select the system with the
optimized characteristics. Simple lattice mixture design was planned for the
optimization using Design-Expert® software. The studied independent variables
were the concentrations of Pluronic L121 (X1), Pluronic P123 (X2) and
Pluronic F127 (X3). Desirability was calculated to choose the optimum
composition with the maximal EE, minimal PS and PDI. The optimized system,
containing 68% w/w Pluronic L121 and 32% w/w Pluronic F127, had the
highest desirability value (0.621).
Entrapment efficiency, particle size, polydispersity index and zeta
potential of the optimized system were 50.74 % ± 3.26, 161.50 ±7.39 nm, 0.21
±0.03 and -22.42 ± 1.72 mV, respectively.
Spherical non-aggregated particles with smooth surface were observed
upon imaging with transmission electron microscope.
In vitro drug release study from the optimized system showed a
significantly longer drug release half-life (6.32 hr) when compared to the
market product (1.6 hr). Almost all the drug has been released after 8 hrs in case
of market product, while just about (69%) of drug released from optimized
system. It took about 48 hrs to release almost all the drug amount in case of
optimized micellar system. So, it could be deduced that the prepared micellar
dispersion achieved the targeted sustained release profile for Vinpocetine.
The optimized system was lyophilized, sterilized and characterized by
differential scanning calorimety )DSC) and infrared spectroscopy (IR). There
was no change or disappearance in the characteristic peak of the drug, indicating
stability of the formula and absence of any physical or chemical change.

Includes CD copy for The Thesis

Text In English and Abstract in Arabic .