The identification of carvedilol was done by FTIR spectroscopy. The UV spectrum was recorded in range 200-400 nm.
Melting point – It was determined in Thiele’s tube using capillary.
The solubility of carvedilol was determined in pH 7.4 phosphate buffer and in pH 7.4 phosphate
Determination of partition coefficient 83:
The partition coefficient of the drugs
was determined using n-octanol as the oil phase and phosphate buffer saline pH
7.4 as the aqueous phase. The n-octanol: phosphate buffer partition coefficient
serves as a parameter lipophilicity.an accurately weighed quantity of each
100mg drug was dissolved in 10 ml of the n-octanol phase and shaken at 370C
for 24 h against 10 ml buffer in a sealed container. The two phases were
separated and then they were analyzed spectro-photometerically
(ShimadzuUV-1800, Japan) for respective drug contents. The partition
coefficient of drug (Ko/w) was calculated using following
Estimation of Carvedilol
Determination of ?max for
To determine the ?max for carvedilol,
the standard solution of carvedilol was prepared in phosphate buffer saline pH 7.4
and scanned in the UV region by using UV spectrophotometer. The ?max
was determined for preparation of the standard curve of carvedilol.
preparation of standard curve of carvedilol
in phosphate buffers saline pH 7.4 .
Carvedilol was dissolve in 10 ml
methanol and volume is made up to 100 ml in volumetric flask with phosphate
buffer saline pH 7.4.1 ml of stock solution (100 mg/ml) was further diluted to get
solutions having concentrations 2mg/ml to 24 mg/ml.
Absorbance of each solution was measured at 285 nm using Shimadzu UV
Spectrophotometer and phosphate buffer pH 7.4 as a reference standard. The standard
curve was generated for entire range from 2 to 24 mg/ml.
FTIR absorption spectra of
carvedilol, polymers (HPMCK15M, PVPK30, and EC) and
physical mixture of carvedilol and polymers was recorded by using FTIR spectrophotometer
(Bruker FTIR ).
Calculation of dose of Carvedilol in the transdermal therapeutic system
The normal dose of Carvedilol is 6.5mg
twice a day orally, the total oral dose of Carvedilol per day is 13 mg.
To develop transdermal therapeutic
system of carvedilol for one day, the total amount of drug to be incorporated
into patch would be 13 mg.
As Carvedilol undergoes extensive
first pass hepatic metabolism, its oral bioavailability is 25-35 %. Since a transdermal therapeutic system
bypasses the hepatic metabolism and drug enters the systemic circulation
directly, the dose in a therapeutic system would be one half of that oral
dose. Therefore the amount of carvedilol
required would be 13/2 = 6.5 mg.
Calculation of the amount of drug for
one circular cast film
Internal diameter of glass mould = 6.0 cm.
Internal surface area of ring = pr2
22/7 x (3.1) 2
Diameter of circular transdermal
patch = 2.0 cm
Area of circular transdermal patch = pr2
22/7 x (1) 2
Therefore, the numbers of circular
transdermal patches prepared from one circular cast film are
[email protected] 10
One transdermal patch contains 6.5mg
of carvedilol, so the circular cast film contains: 10 x 6.5 = 65 mg of
Preparation transedermal patches 84
The transdermal patches of
composition listed in Table were prepared by solution casting technique
employing a glass substrate(Bangles
wrapped with aluminium foil).Membrane type transdermal patches
containing carvedilol prepared using HPMC alone and by using different ratio of
HPMCK15M, PVPK30, and ethyl cellulose. The polymer were
dissolved in suitable solvent mixed well by using magnetic stirrer.Carvedilol
was added slowly to the polymer solution and mixed thoroughly to obtain uniform
solution.PEG-400 and dibutyl pthallate used as a plasticizer. DMSO and tween-80
were used as a penetration enhancer. The polymeric solution was poured into bangles
placed in a level, hard rigid surface. and dried at room temperature in a dust
free environment for 24 hrs. An inverted funnel was placed over the mould to
prevent fast evaporation of the solvent.Patches of 2.0 cm diameter were prepared
by cutting and packed in an
Drug( mg )