PREPARATION AND IN-VITRO EVALUATION OF

PROLIPOSOME OF ALBENDAZOLE

Supervised By Submitted By
Mr.Shankar Lal Soni Deepak Kumar
(Associate Professor) ( M. Pharm. Pharmaceutics )
Arya College of Pharmacy Semester IIIrd
Department of Pharmaceutics University Enrol.No.
2013/1076
 Contents

INTRODUCTION
DRUG PROFILE
REVIEW OF LITERATURE
RATIONAL AND OBJECTIVE OF WORK
PLAN OF WORK
EXPERIMENTAL WORK
RESULT AND DISCUSSION
REFERENCES
 INTRODUCTION

• Proliposomes are novel generation of carrier mediated

drug delivery system having several advantages over
conventional liposomes.
• proliposomes as dry, free flowing powders, granular
product that immediately forms a liposomal dispersion on
contact with water or a biological fluid in the body .
• Proliposomes have been employed as a basis for a
number of site-specific drug delivery approaches
• Pro-liposomes help to enhance the dissolution efficiency
of poorly soluble drugs.
COMPONENTS USED FOR THE PREPARATION OF PROLIPOSOMES

• Phospholipids
• Steroids
• Solvents
 Methods of proliposome preparation

• Film- deposition on carrier method

• Spray drying method
• Fluidised-bed method
• Supercritical antisolvent method
 RATIONALE AND OBJECTIVE OF THE STUDY

• Albendazole, methyl [5-(propyl thio)-1-H-benzimidazol-2yl] carbamate, is a

benzimidazole derivative effective in the treatment of echinococcosis, hydatid
cysts and neurocysticercosis. It demonstrates variable, unpredictable and low
therapeutic response (20% to 50%) in cases of echinococcosis. The probable
reason is Albendazole poor intestinal absorption (5%) due to its low aqueous
solubility.
Therefore the main aim of the study is
• to develop a drug delivery system to deliver Albendazole close to target site,
leading to reduction of dose related side effects.
• to investigate the possibility of obtaining a prolonged, relatively constant
effective level of Albendazole from the proliposome.
• to develop a stable, reproducible and patent non-infringing targeted drug
delivery system for Albendazole.
 Plan of work
• Selection of drug and Lipid
• Preformulation studies
• Drug- i)Organoleptic characterization
ii)Melting Point
iii)Determination of λ max and Standard curve
iv)Solubility of drug
v)Partition coefficient
• Drug-excipients compatibility study
• Preparation of formulations
• Evaluation of optimized proliposome- i. Appearance and Percentage Yield
ii.Particle Size
iii.Percentage drug entrapment
iv.In Vitro drug release study
v.In-vitro drug release kinetic study
vi.Transmission electron microscopy
 Drug Profile
• Discription: Albendazole is a broad-spectrum, synthetic benzimidazole-derivative anthelmintic.
• Synonyms: Albendazol, Albendazole, Albendazolum, Eskazole
• Chemical Names: (5-(propylthio)-1H-benzimidazol-2-yl)carbamic acid methyl ester
• IUPAC Name: methyl N-(6-propylsulfanyl-1H-benzimidazol-2-yl)carbamate
• Molecular Formula: C12H15N3O2S
• Molecular Weight: 265.331 g/mol
• Solubility: Practically insoluble in water
• LogP: 2.7
• Mechanism of Action: Albendazole causes degenerative alterations in the tegument and intestinal cells of
the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or
assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake
of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores.
Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the
subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which
is the energy required for the survival of the helminth. Due to diminished energy production, the parasite
is immobilized and eventually dies.
• Absorption: Poorly absorbed from the gastrointestinal tract due to its low aqueous solubility.
• Plasma Protein binding: 70% bound to plasma proteins
• Bioavailability: Oral bioavailability of Albendazole appears to be increased when the drug is administered
with a fatty meal
• Metabolism: Hepatic.
• Uses: Mesh Headings: anthelmintics, anticestodalagents, antiprotozoal agents.
 Preformulation

1. Physical Appearance-
• Colour-Colorless crystals
• Odor-Odorless
• Form-Crystalline
• Taste-Bitter
2.Melting point of drug - 208.66±0.577 °C
3.Partition coefficient of drug- 3.49±0.722
 4.UV-VIS spectra
4. λ max of Albendazole in Methanolic glacial acetic acid
was determined by using UV-visible spectrophotometer and
Drug exhibited maxima at 235 nm.
Calibration curve of Albendazole in Methanolic glacial
acetic acid (λmax = 235 nm)

y = 0.1058x + 0.038
Calibration curve in Methanolic R² = 0.9993
glacial acetic acid at 231nm, 9,
Calibration curve 0.981666667
in Methanolic
glacial acetic acid at 231nm, 8,
0.894
Calibration curve in Methanolic
glacial acetic acid at 231nm, 7, Calibration curve in Methanolic glacial acetic acid at
Absorbance

0.771
Calibration curve in Methanolic 231nm
glacial acetic acid at
Calibration curve in Methanolic 231nm, 6, 0.67
glacial acetic acid at 231nm, 5,
Calibration curve 0.579333333
in Methanolic
glacial acetic acid at 231nm, 4,
Calibration curve in Methanolic
0.463
glacial acetic acid at 231nm, 3, Linear (Calibration curve in Methanolic glacial acetic
Calibration curve 0.360333333
in Methanolic acid at 231nm)
glacial acetic acid at 231nm, 2,
0.247
Calibration curve in Methanolic
glacial acetic acid at 231nm, 1,
0.137

Concentration(µg/ml)
5.Solubility studies of Albendazole in solvents

Sr. No. Solvent Solubility (mg/ml)

1 Methanol 5.198±0.00945

2 Diethyl ether 0.0475±0.0001

3 Acetone 0.249±0.00144

4 1N HCL 75.77±0.23786

5 DCM 4.26±0.0144

6 Ethanol 5.712±0.00016

7 Distilled water 0.0137±0.00016

 REFRENCES

1. Singh, R. and J. W. Lillard, Jr. (2009). "Nanoparticle-based targeted drug delivery." Exp Mol Pathol 86(3): 215-223.
2. Lim, S. B., A. Banerjee, et al. (2012). "Improvement of drug safety by the use of lipid-based nanocarriers." J Control Release 163(1): 34-45.
3. Onyuksel, H., F. Sejourne, et al. (2006). "Human VIP-alpha: a long-acting, biocompatible and biodegradable peptide nanomedicine for essential hypertension."
Peptides 27(9): 2271-2275.
4. Rawat, M., D. Singh, et al. (2008). "Lipid carriers: a versatile delivery vehicle for proteins and peptides." Yakugaku Zasshi 128(2): 269-280.
5. B.R. Lentz, T.J. Carpenter, D.R. Alford, Spontaneous fusion of phosphatidylcholine vesicles in the fluid phase, Biochemistry 26 (1987)
5389–5397.
1. G.V. Betageri, Proliposomal Drug Delivery System, US Patent 6, 849,269, 2005.
2. A. Arien, B. Dupuy, Encapsulation of calcitonin in liposomes depends in the vesicle preparation method, J. Microencapsul. 14 (1997) 753–760.
3. A.M. Al-Meshal, Oral administration of liposomes containing cyclosporine: a pharmacokinetic study, Int. J. Pharm. 168 (1998) 163–168.
4. H. Xu, L. He, S. Nie, J. Guan, X. Zhang, X. Yang, W. Pan, Optimized preparation of vinpocetineproliposomes by a novel method and in vivo evaluation of its
pharmacokinetics in New Zealand rabbits, J. Control. Release 140 (2009) 61–68.