1. A Seminar on Pharmacosomes
By:
Shakeel Shaikh Shaikh Quader
M.Pharm (Pharmacuetics)
shakeelpharma4@gmail.com
Under the Guidance of
Prof. Siraj Shaikh
HOD of Pharmacuetics
Ali Allana COP Akkalkuwa
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4. vMost of the drugs, particularly chemotherapeutic agents, have
shown to have narrow therapeutic window, and their clinical
use is limited. Thus, their therapeutic effectiveness may be
increased by incorporating them in an advantageous manner. In
the past few decades, considerable attention had been focused
on the development of novel drug delivery system (NDDS).
v Lipid based drug delivery systems have been examined in
various studies and exhibited their potential in controlled and
targeted drug delivery. Pharmacosomes, a novel vesicular drug
delivery system, offering a unique advantage over liposomes
and niosomes, and serve as potential alternative to these
conventional vesicles.
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5. üPharmacosomes are the colloidal dispersions of drugs covalently
bound to lipids, and may exist as ultrafine vesicular, micellar, or
hexagonal aggregates, depending on the chemical structure of drug-
lipid complex.
üAs the system is formed by binding the drug (pharmakon) to carrier
(soma), they are termed as pharmacosomes.
üThe development of pharmacosomes depend upon the bulk and
surface interaction of the lipids with the particular drug.
üAny drug having the active hydrogen atom like –COOH, -OH, -
NH2 etc are esterified to lipid with or without help of spacer chain
which strongly result in the formation of amphiphilic compound, that
can help in the cell wall transfer in the organism.
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7. ü Pharmacosomes impart better biopharmaceutical
properties to the drug, resulting in improved
bioavailability.
ü Pharmacosomes have been prepared for various non-
steroidal anti-inflammatory drugs, proteins,
cardiovascular and antineoplastic drugs.
ü Developing the pharmacosomes of the drugs has been
found to improve the absorption and minimize the
gastrointestinal toxicity.
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8. Advantage of Pharmacosomes
1. No leaching of drug takes place because the drug is
covalently bound to the carrier.
2. Drugs can be delivered directly to the site of infection.
3. Drug release from pharmacosomes is generally
governed by hydrolysis (including enzymatic).
4. Their degradation velocity into active drug molecule,
after absorption depends on their size and functional
groups of the drug molecule, the chain length of the
lipids, and spacer.
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9. 5. Reduced cost of therapy.
6. Suitable for both hydrophilic and lipophilic drugs. The
aqueous solution of these amphiphiles exhibits
concentration dependant aggregation.
7. High and predetermined entrapment efficiency of drug
and carrier are covalently linked together.
8. Volume of inclusion doesn’t influence on entrapment
efficiency.
9. No need of removing the free un-entrapped drug from
the formulation which is required in case of liposomes.
10. Improves bioavailability especially in case of poorly
soluble drugs.
11.Reduction in adverse effects and toxicity.
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10. 1. Pharamcosomes have some importance in escaping the tedious
steps of removing the free unentrapped drug from the
formulation.
2. Pharmacosomes provide an efficient method for delivery of drug
directly to the site of infection, leading to reduction of drug
toxicity with no adverse effects and also reduces the cost of
therapy by improved bioavailability of medication, especially in
case of poorly soluble drugs.
3. Pharmacosomes are suitable for incorporating both hydrophilic
and lipophilic drugs.
4. Entrapment efficiency is not only high but predetermined,
because drug itself in conjugation with lipids forms vesicles.
5. There is no need of following the tedious, time-consuming step
for removing the free, unentrapped drug from the formulation.
Important
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11. 6. Since the drug is covalently linked, loss due to leakage of drug,
does not take place.
7. No problem of drug incorporation
8. Encaptured volume and drug-bilayer interactions do not
influence entrapment efficiency, in case of pharmacosomes.
9. In pharmacosomes, membrane fluidity depends upon the phase
transition temperature of the drug lipid complex, but it does not
affect release rate since the drug is covalently bound.
10. The drug is released from pharmacosome by hydrolysis
(including enzymatic).
11. The physicochemical stability of the pharmacosome depends
upon the physicochemical properties of the drug-lipid complex.
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13. Components used for the formulation of
pharmacosomes
There are three essential components for pharmacosomes
preparation.
Drugs
Drugs containing active hydrogen atom (-COOH, OH, NH2)
can be esterified to the lipid, with or without spacer chain and
they form amphiphilic complex which in turn facilitate
membrane, tissue, cell wall transfer in the organisms.
Solvents
For the preparation of pharmacosomes, the solvents should
have high purity and volatile in nature. A solvent with
intermediate polarity is selected for pharmacosomes
preparation.
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14. Lipids
Phospholipids are the major structure component of
biological membranes, where two types of phospholipids
such as phosphoglycerides and spingolipids are generally
used. The most common phospholipid is phosphotidyl
choline moiety. Phosphotidyl choline is an amphiphilic
molecule in which a glycerol bridges links a pair of
hydrophobic acyl hydrocarbon chains, with a hydrophilic
polar head group phosphocholine.
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17. This method produce multilamellar vesicle with a large
diameter.
The lipophilic surfactant like span 40, span 60, span 80,
cholesterol and diacetyl phasphate can also be used in
hand shaking method.
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21. Drug salt was converted into the acid form to provide an active
hydrogen site
for complexation.
Drug acid was prepared by acidification of an aqueous solution
of drug salt, extraction into chloroform, and subsequent recrystallization.
Drug -PC complex was prepared by associating drug acid with an
equimolar
concentration of PC.
The equimolar concentration of PC and drug acid were placed in a 100-
mL round bottom flask and dissolved in dichloromethane.
The solvent was evaporated under vacuum at 40°C in a rotary vacuum
evaporator.
The pharmacosomes were collected as the dried residue and placed in a
vacuum desiccator overnight and then subjected to characterization.
Formulation of pharmacosomes:
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22. Pharmacosomes are evaluated for the following parameters.
Solubility:
To determine the change in solubility due to complexation,
solubility of drug acid and drug-PC complex was determined in pH
6.8 phosphate buffer and n-octanol by the shake-flask method.
Drug acid (50 mg) (and 50 mg equivalent in case of complex)
was placed in a 100-mL conical flask. Phosphate buffer pH 6.8 (50
mL) was added and then stirred for 15 minutes.
The suspension was then transferred to a 250 mL separating
funnel with 50 mL n-octanol and was shaken well for 30 minutes.
Then the separating funnel was kept still for about 30 minutes.
Concentration of the drug was determined from the aqueous layer
spectrophotometrically at 276 nm.
Evaluation of pharmacosomes:
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24. Differential scanning calorimetry (DSC):
Thermograms of drug acid, phosphatidylcholine (80 %) and the
drug -PC complex were recorded using a 2910 Modulated
Differential Scanning Calorimeter V4.4E (TA Instruments, USA).
The thermal behavior was studied by heating 2.0 ± 0.2 mg of
each individual sample in a covered sample pan under nitrogen gas
flow. The investigations were carried out over the temperature
range 25–250 °C at a heating rate of 10 °C min–1.
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25. X-ray powder diffraction (XRPD):
The crystalline state of drug in the different samples was
evaluated using X-ray powder diffraction. Diffraction
patterns were obtained on a Bruker Axs- D8 Discover
Powder X-ray diffractometer, Germany.
The X-ray generator was operated at 40 kV tube
voltages and 40 mA tube current, using lines of copper as
the radiation source. The scanning angle ranged from 1 to
60° of 2q in the step scan mode (step width 0.4° min–1).
Drug acid, phosphatidylcholine 80 % (Lipoid S-80) and
the prepared complex were analyzed.
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28. Applications:
§ Targeted Drug delivery:
§ Delivery of Peptide drug:
§ E.g: 9-desglycinamide, 8-arginine vasopressin.
§ Carrier for FB
§ Development of Novel ophthalmic DDS
§ Pharmacosomes elicit greater shelf stability.
§ The approach has successfully improved the therapeutic
performance of various drugs i.e. pindolol maleate,
bupranolol hydrochloride, taxol, acyclovir, etc.
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29. The phase transition temperature of pharmacosomes in the
vesicular and Micellar state could have significant influence
on their interaction with membranes.
Pharmacosomes can interact with bimembranes enabling a
better transfer of active ingredient. This interaction leads to
change in phase transition temperature of bimembranes
thereby improving the membrane fluidity leading to enhance
permeations.
Pharmacosomes have greater degree of selectivity for action
on specific target cells.
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30. Drug Therapeutic Application of
Drugs after incorporation
with Pharmacosomes.
Pindolol diglyceride Three to five fold increase in
plasma concentration Lower
renal clearance [
Amoxicillin Improved cytoprotection and
treatment of H.pylori infections
in male rats.
Taxol Improved biological activity
Cytarbin Improved biological activity
Dermatan sulfate Improved biological activity
Bupranolol hydrochloride Enhanced effect on intraocular
pressure.
Enhance lymph transport
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31. Conclusion:
Vesicular systems have been realized as extremely useful carrier
systems in various scientific domains. Over the years, vesicular
systems have been investigated as a major drug delivery system,
due to their flexibility to be tailored for varied desirable purposes.
In spite of certain drawbacks, the vesicular delivery systems still
play an important role in the selective targeting, and the controlled
delivery of various drugs. Researchers all over the world continue
to put in their efforts in improving the vesicular system by making
them steady in nature, in order to prevent leaching of contents,
oxidation, and their uptake by natural defense mechanisms.
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