1. Experiment No: 10 DATE: / /
Aim: To Formulate and Evaluate Osmotically Controlled Drug Delivery System.
REQUIREMENTS:
Chemicals: Metoprolol tartrate, Mannitol, MCC, Mg-stearate, Cellulose acetate, PEG 400,
Acetone
Apparatus: Tablet compression machine, Dissolution test apparatus, hardness tester, Varner
capillary
Reference:
1. J. Pharm. Res. Vol. 5. No. 2. April 2006. P=34
2. Ind. J. Pharm. Sci. May – June 2006, P= 295-300.
3. J. Pharm. Sci. Vol. 96. No. 5. May 2007. P= 1008
Theory:
Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or
systemically, for a specified period of timeThese systems are capable of controlling the rate
of drug delivery, sustaining the duration of therapeutic efficacy, and/or targeting the
delivery of drug to a tissue.These are able to specify the release rate and duration in vivo
precisely, on the basis of simple in vitro tests.Controlled release is perfectly zero order
release that is the drug release over time irrespective of concentration.
Release of drug from the delivery systems is activated by some physical, chemical, or
biochemical processes and facilitated by the energy supplied externally.The rate of drug
release is then controlled by regulating the process applied or energy input.
Based on the nature of the process applied or the type of energy used, these activation
modulated DDS can be classified into:
■ Physical means
■ Chemical means
■ Biochemical means
1. Physical means
a) Osmotic pressure-activated DDS
b) Hydrodynamic pressure-activated DDS
c) Vapour pressure-activated DDS
d) Mechanically activated DDS
e) Magnetically activated DDS
f) Sonophoresis-activated DDS
g) Iontophoresis-activated DDS
h) Hydration-activated DDS
2. Chemical means
a) PH activated DDS
b) Ion activated DDS
c) Hydrolysis activated DDS
2. 3. Biochemical means
a) Enzyme activated DDS
b) Biochemical activated DDS
OSMOTIC PRESSURE DDS-□In this type, drug reservoir can be either solution or
solid formulation contained within semi-permeable housing with controlled water
permeability.The drug is activated to release in solution form at a constant rate through a
special delivery orifice.
The rate of drug release is modulated by controlling the gradient of osmotic pressure.The
drug release is activated by osmotic pressure and controlled at a rate determined by the
water permeability and the effective surface area of the semi-permeable housing as well
as the osmotic pressure gradient.
Where,
Q/t – rate of drug release
Pw – permeability of semipermiable housing Am -effective S.A. of semipermiable
housing hm – thickness of semipermiable housing
(πs-πe) – differential osmotic pressure between the drug delivery system with osmotic
pressure πs & the environment with osmotic pressure πe.
What is osmotic pressure?
Osmotic pressure is a most important colligative property according to pharma point of
view. Colligative property is the concentration of solution independent of solute property.
Osmotic pressure of a solution is the external pressure that must be applied to the solution in
order to prevent it being diluted by the entry of solvent via a process known as Osmosis. Such
membrane is only permeable to solvent molecule. Because only solvent can pass through the
semi permeable membrane, the driving force for the osmosis arises from the inequity of the
chemical potentials of the solvent on opposing side of the membrane.
Application of osmotically controlled drug delivery system:
Advantage of osmotically drug delivery system
• The zero-order drug release rate is achievable with osmotically controlled drug
delivery system.
• Higher release rates are possible with osmotic systems compared with conventional
diffusion-controlled drug delivery systems.
3. • The release rate of osmotic systems is highly predictable and can be programmed by
modulating the release control parameters.
• Drug release is independent of gastric pH and hydrodynamic condition.
• The release mechanisms are not dependent on drug.
• A high degree of in-vitro and in-vivo correlation (IVIVC) is obtained in osmotic
systems.
• The rationale for this approach is that the presence of water in gastric region is
relatively constant, at least in terms of the amount required for activation and
controlling osmotically base technologies.
Disadvantage of osmotically drug delivery system
• Slightly higher cost than matrix tablet or multi particulates ion capsule dosage form.
• Gastro intestinal obstruction cases have been observed with the patient receiving
Nifedipine tablet.
• Another case was reported for osmosin (Indomethacin OROS) is frequent occurrences
of serious gastrointestinal reaction were observed leading to osmosin withdrawal.
• Magnetic resonance imaging (MRI) of tablet elucidates that non-uniform coating
leadsto different pattern of drug release among the batches.
• If the coating process is not well controlled there is a risk of film defects, which
results in dose dumping
• Size hole is critical
• Dose dumping
• Retrival therapy is not possible in the case of unexpected adverse events
Need For Developing Odds Dosage Form :
1. In Order To Reduce The Dose
2. To Decreases Dose Related Side Effects
3. To Minimizes Rate Of Administration
4. To Provide Controlled Release And
5. To Increase Patient Compliance.
FORMULATION OF OSMOTIC DDS: (Metoprolol tartrate)
Ingredients Qty given (mg) Qty.taken(gm) = 50 Tab.
Drug (Metaprolol) 100 5
Mannitol 50 2.5
4. Microcrystalline cellulose 150 7.5
Magnesium stearate 3 0.150
Talc 3 0.150
METHODOLOGY:
Method of Preparation of Core Tablets
Mannitol was used as osmogent in this formulation because other osmogents like
sodium chloride,potassium chloride, magnesium sulphate, etc. Are inorganic water soluble
osmogent.
Metoprolol tartrate is antihypertensive drug. In hypertension inorganic salts are
restricted because this salt increases hypertension. Also, mannitol is directly compressible
and having good osmogenic property. So, mannitol was used as osmogent. The batches were
prepared by direct compression technique.
The ingredients were individually passed through 40# and mixed for 15 minute in
mortar and pestle as per the The blend was again passed through was compressed into tablets
using single punch tablet machine.
Method of Preparation of Polymeric Coating Solution
Coating polymer Eudragait (2 %) was hydrated in acetone.
The solution was stirred for 15 min.
Plasticizer (PEG 400) (20%) was added into the polymeric solution Cellulose acetate and
Plasticizer (PEG 400) quantity was selected as per trial and error method.
The solution of color (Sudan red III) in acetone was gradually mixed with the resultant
polymeric solution for 80-100 RPM using Remi magnetic stirrer bath.
At the end pass the filtrate through the sieve of fine pore diameter so that if any insoluble
particle if remained in the coating solution will get removed.
EVALUATION:
Hardness Test
Tablet dimension (diameter and thickness), and crushing strength of randomly selected
Tablets were determined using Monsento Hardeness tester.
Friability Test
For each formulation, 20 tablets were weighed. The tablets were placed in a
friabilator (Roche Friabilator) and subjected to 100 rotations in 4 minutes. The tablets
5. were then dedusted and reweighed. The friability was calculated as the percentage weight
loss.
In Vitro Dissolution study
Dissolution test was performed using a USP paddle apparatus at 370C ±0.50C in 900 ml of
pH 6.8 phosphate buffer with a speed of 100 rpm. Samples were withdrawn after
predetermined time intervals and metoprolol tartrate content was measured using a
spectrophotometer (model UV-1700 Pharmaspec, UV-Visible Spectrophotometer, at a
wavelength 275nm
RESULT:-
