Country /Region
|
Regulatory Agency
|
|
1
|
United States of America
|
United States Food and Drug Administration (USFDA)
|
2
|
United Kingdom
|
Medicines and Healthcare products Regulatory Agency (MHRA)
|
3
|
European Union
|
European Medicines Agency (EMA)
|
4
|
European Union
|
European Directorate for the Quality of Medicines (EDQM)
|
5
|
Australia
|
Therapeutic Goods Administration (TGA)
|
6
|
Japan
|
Pharmaceutical and Medical Devices Agency (PMDA)
|
7
|
Canada
|
Therapeutic Products Directorate (TPD) in
Health Product and food branch (HPFB) of Health Canada (HC)
|
8
|
France
|
Agence Francaise de Securite Sanitaire des Produits de
Sante (AFSSAPS)
Translated into English as- French Agency for the Safety of Health Products
|
9
|
Germany
|
Bundesinstitut für Arzneimittel und
Medizinprodukte, (BfArM)
Tanslated into English as- Federal Institute
for Drugs and Medical Devices
|
10
|
Brazil
|
Agência Nacional de Vigilância Sanitária (ANVISA)
Tanslated into English as- The National Health Surveillance Agency
|
11
|
India
|
Drugs Controller General of India (DCGI) who heads
Central Drugs Standard Control Organisation (CDSCO)
|
12
|
Switzerland
|
Swiss Agency for Therapeutic Products (SWISSMEDIC)
|
14
|
Singapore
|
Health Sciences Authority (HSA)
|
15
|
New Zealand
|
New Zealand Medicines and Medical Devices Safety Authority
(MEDSAFE)
|
Friday, 30 August 2013
Famous Drug Regulatory authorities in the world
Thursday, 29 August 2013
BRIEFING THE FORMULATION OF CONTROLLED RELEASE DOSAGE FORMS
CONTROLLED RELEASE DOSAGE FORMS –
Controlled release dosage forms are the pharmaceutical dosage
forms which release the drug slowly into the systemic circulation and thereby
it prolong the pharmacological activity of the drug.
The advantages of Controlled release dosage forms over the
conventional dosage forms –
1)
To
reduce the frequency of dosing
2)
To
increase the patient compliance
When we will go for designing a Controlled release dosage is –
1)
When
the drug is having very short biological half – life
2)
When
the drug is stable in both the acidic and basic pH in the GIT
3)
When
the drug is absorbed into the systemic circulation throughout the GIT
Materials used for formulating a Controlled release dosage
forms –
1)
Controlled
release polymers (both Hydrophilic and Hydrophobic polymers) as matrix systems
2)
Converting
the drug molecules into low water soluble salts (for example - conversion of water
soluble salts likes hydrochlorides and sulfates into low water soluble salts
like stearates)
3)
Osmotic
pump systems and many more
Formulation development of a Controlled release dosage form
using Controlled release polymers (both Hydrophilic and Hydrophobic) as matrix
systems –
Let us take an example and explore the way to formulate
Matrix is a non - retardant material which prevents the
release of drug from the system. Let us take Propranolol Hydrochloride as a
drug molecule and HPMC (K100 M), (K50 M) and Ethyl Cellulose as matrix formers
Propranolol Hydrochloride is highly soluble and highly
permeable drug which comes under BCS – I Classification. It is absorbed into
the systemic circulation throughout the GIT. It is having short biological half
– life of about 3.5 hours and requires more than 3 doses per day in some
patients.
HPMC (K100 M) and HPMC (K50 M) are Hydrophilic bio - polymers
whose viscosity is 10,00,000 Cps and 50,000 Cps respectively. We are taking the
polymers of this high viscosity in order to control the release if we take the
HPMC with lower viscosity grade it will not control the release due to its low
viscosity and low gelling nature. Whenever the gelling nature is low the
polymer get eroded soon and the drug is released rapidly into the systemic
circulation.
Ethyl Cellulose is a Hydrophobic polymer and it is porus and
it is generally mixed with Hydrophilic polymers to retard the release from the
matrix of Hydrophilic polymers
Take Microcrystalline cellulose as diluents (Avicel pH 102)
Take Magnesium stearate as Lubricant.
Develop several formulations varying the ratio of drug : polymer
and the overall weight is adjusted using diluent.
Perform stability studies keeping the powder mixture of
different formulations in vials and stored at 30 ± 20 C and 75 ± 5 %
RH for 60 days and performed FTIR analysis on those samples for evaluating the
drug – excipient compatability.
Perform Pre – compression studies like Bulk density, Tap
density, Hausner’s ratio and Carr’s Index and found that the powder mixture of
different formulations and found that the powder is having very poor flow properties.
Hence there is no chance for Direct compression method.
We can’t go for wet granulation method using purified water as
granulating agent because these Hydrophilic polymers will absorb water and
swell. Hence, we can’t go for wet granulation method using purified water.
Next alternate is to go for wet granulation method using any
organic solvent like Isopropyl Alcohol as granulating agent.
Pass all the ingredients through sieve number 20 separately.
Take these ingredients according to their ratio’s in different formulations in
a mortar and pestle and mixed thoroughly. While mixing added Isopropyl Alcohol slowly
until granulation consistency is achieved. The obtained blend is passed through
sieve number 12 and dried them in a hot air oven.
Later the dried granules are passed through sieve number 16.
If the obtained granules are big in size and if we punch the
tablets the tablets may break as laminates. If the obtained granules are small
in size and if we punch the tablets the tablets will have high hardness.
Hence, we needed granules with average size and some small
granules to fill the gaps between the compressed material during punching.
The tablets are obtained with required hardness and some of
them are charged for stability studies and dissolution is performed on some
tablets. The tablets shows extending the release for 24 hours.
If the tablets don’t shows extending the release upto 24
hours then use Ethyl cellulose in different ratios in the formulation and try
to prolong the release.
There is no marketed controlled release formulation for this Propranolol
Hydrochloride hence we cannot able to caliculate f2 value.
Sunday, 11 August 2013
Tuesday, 19 March 2013
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