Formulation and Evaluation of Fast Dissolving Tablets of Doxazosin Mesylate
Mukul Ahmed1, Ravikumar2*, Narayanaswamy VB3, Injamamul Haque1, Mohibul Hoque4
1M.Pharm (Pharmaceutics), Research Scholar, Karavali College of Pharmacy, Mangalore
2Department of Pharmaceutics, Karavali College of Pharmacy, Mangalore
3Department of Pharmacognosy, Karavali College of Pharmacy, Mangalore
4Department of Pharmacology, Karavali College of Pharmacy, Mangalore
*Corresponding Author E-mail: ravikumar300@gmail.com
ABSTRACT:
The objective of this research was to formulate fast dissolving tablets of Doxazosin mesylate that disintegrate in the oral cavity upon contact with saliva and there byimprove therapeutic efficacy. Doxazosin mesylate is used for the treatment of the signs and symptoms of benign Prostatic Hyperplasia. Fast dissolving tablets ofDoxazosin mesylate were prepared by direct compression method using superdisintegrant addition method, by using sublimation method and effervescent method. Thirty two formulations were prepared and evaluated for hardness, thickness, friability, weight variation, drug content, in vitro disintegration time, in vitro dispersion time, wetting time, water absorption ratio and in vitro dissolution studies.
FTIR and DSC studies revealed that there was no chemical interaction between the drug and the excipients. Formulation S8 was found to be the best on the basis of wetting time, in vitro disintegration time and in vitro drug release. The formulation S8containing camphor (8%) as subliming agent was found to be the optimized combinations. Stability studies were carried out at 250C±20C/60%±5% RH and400C±20C/75%±5% RH for formulation S8 for 60 days. The results of stability studies indicated no significant changes with respect to physicochemical properties, in vitro disintegration time, wetting time and in vitro drug release.
KEY WORDS: Fast dissolving tablets, Doxazosinmesylate, Superdisintegrant, Directcompression, Sodium starch glycollate, camphor, citric acid.
INTRODUCTION:
Tablet is the most widely used dosage form because of its convenience in terms of self-administration, compactness and ease in manufacturing. Patients often experience difficulty in swallowing conventional tablets when water is not available nearby. These are novel types of tablets that dissolve/ disintegrate/ disperse in saliva within few seconds without water. According to European pharmacopoeia, these MDTs should dissolve/ disintegrate in less than three minutes. The formulation is more useful for the bed ridden and patients who have the swallowing problem. The benefits of MDTs is to improve patients compliance, rapid onset of action, increased bioavailability and good stability which make these tablets popular as a dosage form of choice in the current market1-2.
United States Food and Drug Administration (US FDA) defined fast dissolving tablet (FDT) as “A solid dosage form containing medicinal substance or active ingredient which disintegrate rapidly usually within a matter of seconds when placed up on the tounge”3.
Doxazosin mesylate is a quinazoline compound that is a selective inhibitor of the alpha1 subtype of alpha-adrenergic receptors. The chemical name of doxazosinmesylate is 1-(4-amino-6, 7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methane sulfonate. The empirical formula for doxazosinmesylate is C23H25N5O5•CH4O3S and the molecular weight is 547.6.
Doxazosin mesylate is freely soluble in dimethyl sulfoxide, soluble in dimethyl formamide, slightly soluble in methanol, ethanol, and water (0.8% at 25°C), and very slightly soluble in acetone and methylene chloride. Cardura is available as coloured tablets for oral use and contains 1 mg (white), 2 mg (yellow), 4 mg(orange) and 8 mg (green) of doxazosin as the free base.
In the present study an attempt was made to formulate Doxazosin mesylate fast dissolving tablets and to investigate the effect of subliming agent on the release profile of the drug in the tablets. Hence formulating Doxazosin mesylate fast dissolving tablets leading to an increase in bioavailability of the drug, quick onset of pharmacological action and increase in patient compliance due to ease of administration.
MATERIALS AND METHODS:
Materials:
Doxazosin mesylate was obtained as gift sample from Aurobindo Pharma Pvt. Ltd. Hyderabad. All other materials, excipients, solvents and reagents were either analytical or Pharmacopoeial grade were procured from Zydus Research Centre, Ahmadabad and S.D. fine Chemicals Mumbai.
Methods:
Drug- polymer interaction studies:
Fourier Transform Infra-Red (FT-IR) spectral analysis:
Excipients are integral components of almost all pharmaceutical dosage forms. The successful formulation of a stable and effective solid dosage form depends on the careful selection of the excipients, which are added to facilitate administration, promote the consistent release and bioavailability of the drug and protect it from degradation. Infra-Red spectroscopy is one of the most powerful analytical techniques to identify functional groups of a drug.
Compatibility of Doxazosin mesylate with superdisintegrants and diluents was established by infrared spectral analysis. The samples were mixed with potassium bromide in a ratio of 1:99 in agate mortar and pestle and mixed thoroughly. This mixture was then loaded in FTIR to get an IR spectrum. IR Spectral analysis was carried out to investigate the changes in chemical composition of the drug after combining it with the excipients.
Differential Scanning Calorimetry (DSC) analysis
DSC analysis was performed using Shimadzu DSC-60, Shimadzu Limited Japan. A1:1 ratio of drug and excipient was weighed into aluminium crucible. And sample was analysed by heating at a scanning rate of 200C over a temperature range 40-4300Cunder nitrogen environment.
Preparation of doxazosin mesylateodts:
Doxazosin mesylate tablet can be prepared using three approaches by Direct Compression method.
Approach 1: Sublimation method
Approach 2: Effervescent method
Approach 3: Superdisintegrant addition method
1. Preparation of orodispersible tablets using sublimation method:
Sublimating agents resulted in rapid disintegration of tablets due to the phenomenon of sublimating which improves dissolution. Specified quantity of Doxazosin mesylate and other excipient according to formula given in the table 1 were weighed and passed through 60# screen prior to mixing. All the materials were transferred to mortar and triturated till the mixture was uniform. The resulting powder mixture was compressed into tablets using ten stations Cemach tablet compression machine. The tablets were dried at 600C in oven till constant weight obtain.
2. Preparation of Doxazosinmesylate tablets using Effervescent method
Fast dissolving tablets were prepared by using citric acid and sodium-bi-carbonate in combination in (1:2 ratio) with other excipients shown in table 2 was co-grounded in glass pestle glass mortar. These tablets contain (1-5% w/w) effervescent agent. The drug and microcrystalline cellulose were mixed in small portion of both at each time and blended to get a uniform mixture and kept aside. Then the other ingredients were weighed and mixed in geometrical order and the tablets were compressed using flat face 6.3 mm size punch to get a tablets of 100 mg weight using ten station Cemach tablet compression machine.
Table 1: Composition of Doxazosin mesylate FDT’s using sublimation method
|
INGREDIENTS (mg/tablets) |
FORMULATIONS |
|||||||||||
|
S1 |
S2 |
S3 |
S4 |
S5 |
S6 |
S7 |
S8 |
S9 |
S10 |
S11 |
S12 |
|
|
Doxazosin Mesylate |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Thymol |
2 |
4 |
6 |
8 |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
|
Camphor |
-- |
-- |
-- |
-- |
2 |
4 |
6 |
8 |
-- |
-- |
-- |
-- |
|
Menthol |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
2 |
4 |
6 |
8 |
|
Avicel pH 102 |
64 |
62 |
60 |
58 |
64 |
62 |
60 |
58 |
64 |
62 |
60 |
58 |
|
Aspartame |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Mannitol |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
|
Magnesium Stearate |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Talc |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Orange flavour |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Total weight (mg) |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
Table 2: Composition of Doxazosin mesylate FDT’s using effervescent method
|
INGREDIENTS (mg/tablets) |
FORMULATIONS |
||||
|
E1 |
E2 |
E3 |
E4 |
E5 |
|
|
Doxazosinmesylate |
4 |
4 |
4 |
4 |
4 |
|
Citric Acid |
0.33 |
0.66 |
1.00 |
1.32 |
1.65 |
|
NaHCO3 |
0.67 |
1.34 |
2.00 |
2.68 |
3.35 |
|
Avicel pH 102 |
65 |
64 |
63 |
62 |
61 |
|
Aspartame |
4 |
4 |
4 |
4 |
4 |
|
Mannitol |
20 |
20 |
20 |
20 |
20 |
|
Magnesium stearate |
2 |
2 |
2 |
2 |
2 |
|
Talc |
2 |
2 |
2 |
2 |
2 |
|
Orange flavour |
2 |
2 |
2 |
2 |
2 |
|
Total weight (mg) |
100 |
100 |
100 |
100 |
100 |
3. Preparation of Doxazosin mesylate FDT’s using superdisintegrant method
Doxazosin mesylate tablets each containing 4mg of Doxazosin mesylate were prepared by direct compression method according to formula given in the table 3. The different superdisintegrants used were Sodium starch glycollate, Crosscarmellose sodium and Crosspovidone in different concentrations. Blend was prepared by first passing all the ingredients through 60-mesh sieve separately and collected. The drug and microcrystalline cellulose were mixed in small portion of both at each time and blended to get a uniform mixture and kept aside. Then the other ingredients were weighed and mixed in geometrical order and the tablets were compressed using flat face 6.3 mm size punch to get a tablets of 100 mg weight using ten station Cemach tablet compression machine.
Evaluation of fast dissolving tablets:
Pre-compressional studies4-13
Angle of Repose (Ө):
The angle of repose of API powder was determined by the funnel method. The accurately weighed powder blend was taken in the funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touched the apex of the powder blend. The powder blend was allowed to flow through the funnel freely on to the surface. The diameter of the powder cone was measured and angle of repose was calculated using the following equation.
Ө = tan-1 (h/r)
Where, Ө is the angle of repose, h is the height of pile and r is the radius of the base of pile.
i) Bulk Density and Tapped density:
Loose bulk density (LBD) and tapped bulk density (TBD) of tablet blends were determined using bulk density apparatus. Tablet blend was passed through #18 sieve to break the clumps and transferred to 100ml graduated cylinder. Initial volume was observed. The cylinder was tapped initially 200 times from a distance of 14±2 mm. The tapped volume was measured to the nearest graduated unit. This was repeated for other tablet blends. The LBD and TBD were calculated in g/ml using following formula:
LBD = weight of the powder / volume of the packing
TBD = weight of the powder / tapped volume of the packing
ii) Carr’s Index:
The Compressibility Index of the powder blend was determined by Carr’s compressibility index. It is a simple test to evaluate the BD and TD of a powder and the rate at which it is packed down. The formula for Carr’s Index is as below,
Carr’s Index (%) = [(TBD-LBD) x100]/TBD
Where,
LBD = Loose Bulk Density and TBD = Tapped Bulk Density
iii) Hausner ratio:
The Hausner’s ratio is a number that is correlated to the flowability of a powder or granular material. The Hausner ratio of the powder was determined by the following equation:
Hausner ratio = TBD / LBD
Lower Hausner ratio (<1.25) indicates better flow properties than higher ones (>1.25).
Table 3: Composition of Doxazosin mesylate FDT’s using superdisintegrant addition method
|
INGREDIENTS (mg/tablets) |
FORMULATIONS |
||||||||||||||
|
D1 |
D2 |
D3 |
D4 |
D5 |
D6 |
D7 |
D8 |
D9 |
D10 |
D11 |
D12 |
D13 |
D14 |
D15 |
|
|
Doxazosinmesylate |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Croscarmellose sodium |
1 |
2 |
3 |
4 |
5 |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
|
Sodium starch glycolate |
-- |
-- |
-- |
-- |
-- |
1 |
2 |
3 |
4 |
5 |
-- |
-- |
-- |
-- |
-- |
|
Crosspovidone |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
1 |
2 |
3 |
4 |
5 |
|
Magnesium stearate |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Orange flavour |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Talc |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
2 |
|
Aspartame |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
|
Avicel pH 102 |
65 |
64 |
63 |
62 |
61 |
65 |
64 |
63 |
62 |
61 |
65 |
64 |
63 |
62 |
61 |
|
Mannitol |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
20 |
|
Total weight (mg) |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
100 |
Post-compressional studies:
1. General appearance:
The fast dissolving tablets, morphological characterization which includes size, shape, colour, presence or absence of odour, taste surface texture was determined.
2. Thickness and diameter:
Five tablets were picked from each formulation randomly and thickness and diameter was measured individually. It is expressed in mm and standard deviation was also calculated. The tablet thickness and diameter was measured using vernier calliper.
3. Hardness:
Hardness indicates the ability of a tablet to withstand mechanical shocks while handling. The hardness of the tablets was determined using Monsanto hardness tester. It is expressed in kg/cm2. Five tablets were randomly picked and hardness of the same tablets from each formulation was determined. The mean and standard deviation values were also calculated.
4. Friability test:
Friability test is performed to assess the effect of friction and shocks, which may often cause tablet to chip, cap or break. Roche Friabilator was used for the purpose. Pre-weighed sample of ten tablets were placed in the Friabilator, which was then operated at 25 rpm for 4 minutes or ran up to 100 revolutions. After 100 revolutions the tablets were dusted and reweighed. Compressed tablets should not lose more than 1% of their weight.
The % friability was then calculated by the following formula:
Percentage friability = (Initial weight - Final weight /Initial weight) × 100
5. Weight variation:
20 tablets were selected randomly from each formulation and weighed individually to check for weight variation. The US Pharmacopoeia allows a little variation in the weight of a tablet.
6. Drug content uniformity:
Twenty tablets were weighed and powdered. Powder equivalent to 4 mg drug was transferred into a 100 ml volumetric flask. Volume was made with phosphate buffer pH 6.8. After few minutes the solution was filtered; rejecting first few ml of the filtrate. 10ml of filtrate was taken in a 50 ml volumetric flask and diluted up to the mark with phosphate buffer pH 6.8 and analysed spectrophotometrically at 245 nm. The concentration of Doxazosinmesylate (in µg/ml) was calculated by using the standard calibration curve of Doxazosinmesylate.
vii) Wetting time and water absorption ratio:
A piece of tissue paper folded twice was placed in a small Petridis (i.d = 6.5 cm) containing 6 ml of water. A tablet was placed on the paper and the time required for complete wetting was then measured.
The water absorption ratio, R, was determined using the following equation,
R = Wa - Wb / Wb × 100
Where,
Wb is the weight of the tablet before water absorption and
Wa is the weight of the tablet after water absorption.
viii)In vitro dispersion time:
One tablet was placed in a beaker containing 10 ml of phosphate buffer pH 6.8 at 37 ±0.5ºC and the time required for complete dispersion was determined.
ix) In vitro disintegration time:
In vitro disintegration time was performed by apparatus specified in USP at 50 rpm. Phosphate buffer pH 6.8, 900 ml was used as disintegration medium, and the temperature of which was maintained at 37±2°C and the time in second taken for complete disintegration of the tablet with no palpable mass remaining in the apparatus was measured in seconds.
x) In vitro drug release studies:
In vitro drug release studies were carried out using dissolution apparatus USP type XXIII at 50 rpm. The dissolution medium consisted of 900 ml of Phosphate buffer pH 6.8 maintained at 37±10C. The drug release at different time intervals was measured using a double beam UV Spectrophotometer at 245 nm.
xi) Data Analysis:
Various models were tested for explaining the kinetics of drug release. To analyse the mechanism of the drug release rate kinetics of the dosage form, the obtained data were fitted into zero-order, first order, Higuchi, Korsmeyer-Peppas release model and Hixson-Crowell equation.
xii) Stability Studies:
Stability of a drug has been defined as the ability of a particular formulation, in a specific container, to remain within its physical, chemical, therapeutic and toxicological specifications.
ICH specifies the length of study and storage conditions:
Long term testing 25°C ± 2°C/60%±5% RH for 12 months
Accelerated testing 40°C ± 2°C/75% ±5% RH for 6 months
In the present study, stability studies were carried out at 25°C ± 2°C/60% ±5% RH and 40°C± 2°/75% ± 5% RH for a period of 60 days for the selected formulations (S8). The formulations were then evaluated for changes in the physicochemical properties, wetting time, in vitro disintegration time and in vitro drug release.
RESULTS AND DISCUSSION:
Drug-excipient compatibility studies:
Fourier Transform Infrared (FTIR) Spectroscopy
Doxazosin Mesylate exhibited characteristic peaks attributed to N-H stretching at 3371 cm-1and C=N stretching at 1597 cm-1. The IR spectra of pure drug complied with the reference standard IR spectrum of Doxazosin mesylate which revealed identity to drug sample. Observed frequencies of functional groups present in Doxazosin mesylate were matching with standard theoretical frequencies of functional groups, which confirm identity of Doxazosinmesylate.IR spectral analysis of pure drug sample showed characteristic peaks as shown in figure 1 and Doxazosin mesylate with all ingredients shown in figure 2.
Figure 1: FTIR spectra of Doxazosin mesylate pure drug
Figure 2: FT-IR Spectra of Physical mixture of Doxazosin mesylate + all Excipients
Differential Scanning Calorimetry:
The DSC thermograms of pure Doxazosin mesylate showed melting endothermic peak at 281°C indicating crystalline nature of Doxazosin mesylate, followed by exothermic peak which may be due to decomposition of Doxazosin mesylate. The endothermic peak for the drug in physical mixture, showed minor changes in the melting endotherm of drug (278°C) could be due to the mixing of drug and excipients, which lower the purity of each component in the mixture and May not necessarily indicates potential incompatibility. The result showed that drugs were compatible with excipients. DSC thermograms of drug and physical mixture of drug and excipients were shown in figure 3-4.
Figure 3: DSC thermogram of Doxazosinmesylate
Figure 4: DSC thermogram of Physical mixture of Doxazosinmesylate+ all Excipients
Evaluation parameters
Precompressional parameters:
Powderreadyforcompressioncontainingdrugandvariousexcipientsweresubjectedfor various precompressional evaluation parameters such as bulk density, tapped density, compressibility index, Hausner’s ratio and angle of repose. Pre-compressional parameters (Micrometrics properties) were studied to determine the flow properties of granules, to achieve uniformity of tablet weight. The results of all the preformulation parameters are given table 4 and 5.
The data obtained from angle of repose for the formulations of sublimation method were found to be in the range of 27.52° to 30.28° and for superdisintegrant addition method the range was 27.52° to 32.87°. All the formulations prepared by both the methods showed the angle of repose less than 31°, which reveals good flow property.
Loose bulk density (LBD) for the blend was performed. The loose bulk densities for the formulations of sublimation method varied from 0.49gm/cc to 0.55gm/cc. For superdisintegrant addition method the range was 0.15gm/cc to 0.55gm/cc.
Tapped bulk density (TBD) for the blend was performed. The tapped bulk densities for the formulations of sublimation method varied from 0.61gm/cc to 0.65gm/cc. For superdisintegrant addition method the range was 0.49gm/cc to 0.65gm/cc respectively.
The results of Carr’s consolidation in dexorcompressibility index(%) for the sublimation formulation blend ranged from 13% to 20% and for superdisintegrant addition method it was15%to21.15%.
Hausner ratio of sublimation formulations showed between 1.14 to 1.30 and for superdisintegrant addition method formulations it was 1.14 to 1.26 indicates better flow properties.
Table 4: Pre compression evaluation of Doxazosinmesylate powder using Sublimation method
|
Formulation Code |
Angle of Repose |
Bulk Density (gm/cc) |
Tapped Density (gm/cc) |
Carr’s Index % |
Hausner Ratio |
|
S1 |
26.62±1.035 |
0.418±0.013 |
0.449±0.008 |
6.904±1.046 |
1.074±0.006 |
|
S2 |
28.61±1.241 |
0.399±0.046 |
0.438±0.012 |
8.904±1.143 |
1.097±0.034 |
|
S3 |
25.32±1.146 |
0.401±0.035 |
0.443±0.010 |
9.481±1.135 |
1.105±0.023 |
|
S4 |
27.69±1.253 |
0.395±0.023 |
0.439±0.022 |
10.022±1.146 |
1.111±0.013 |
|
S5 |
27.54±0.846 |
0.403±0.012 |
0.432±0.034 |
6.713±1.234 |
1.071±0.017 |
|
S6 |
28.87±0.955 |
0.399±0.031 |
0.435±0.032 |
8.276±1.124 |
1.090±0.024 |
|
S7 |
29.21±0.866 |
0.407±0.014 |
0.441±0.023 |
7.709±1.146 |
1.084±0.032 |
|
S8 |
28.34±1.244 |
0.371±0.043 |
0.415±0.042 |
10.602±1.134 |
1.119±0.043 |
|
S9 |
27.52±1.136 |
0.389±0.023 |
0.423±0.034 |
8.038±1.152 |
1.087±0.022 |
|
S10 |
26.45±0.957 |
0.391±0.005 |
0.429±0.013 |
8.858±1.098 |
1.065±0.020 |
|
S11 |
27.61±0.697 |
0.401±0.024 |
0.439±0.022 |
8.656±1.153 |
1.095±0.019 |
|
S12 |
29.64±0.957 |
0.379±0.021 |
0.419±0.041 |
10.554±1.136 |
1.106±0.023 |
Table 5: Pre compression evaluation of Doxazosinmesylate powder blend using superdisintegrant addition method
|
Formulation Code |
Angle of Repose |
Bulk Density (gm/cc) |
Tapped Density (gm/cc) |
Carr’s Index % |
Hausner Ratio |
|
D1 |
23.34±1.363 |
0.396±0.012 |
0.424±0.013 |
6.604±1.330 |
1.071±0.012 |
|
D2 |
25.19±1.221 |
0.403±0.015 |
0.429±0.012 |
5.621±1.233 |
1.065±0.024 |
|
D3 |
27.35±1.007 |
0.398±0.023 |
0.417±0.021 |
4.556±1.422 |
1.048±0.013 |
|
D4 |
24.44±1.126 |
0.386±0.004 |
0.409±0.002 |
5.623±1.221 |
1.059±0.015 |
|
D5 |
25.99±1.096 |
0.398±0.013 |
0.427±0.005 |
6.792±1.012 |
1.073±0.010 |
|
D6 |
23.56±1.132 |
0.371±0.025 |
0.395±0.006 |
6.076±1.231 |
1.065±0.003 |
|
D7 |
26.59±1.165 |
0.408±0.034 |
0.436±0.014 |
6.422±1.086 |
1.069±0.006 |
|
D8 |
26.32±1.136 |
0.383±0.013 |
0.405±0.017 |
5.432±1.097 |
1.057±0.016 |
|
D9 |
25.22±1.432 |
0.389±0.017 |
0.421±0.023 |
7.601±1.242 |
1.082±0.027 |
|
D10 |
23.59±1.243 |
0.396±0.006 |
0.434±0.023 |
8.756±1.134 |
1.095±0.010 |
|
D11 |
25.62±0.968 |
0.405±0.023 |
0.429±0.012 |
5.594±1.123 |
1.059±0.015 |
|
D12 |
23.54±0.847 |
0.402±0.005 |
0.429±0.007 |
6.294±1.324 |
1.067±0.023 |
|
D13 |
24.65±1.166 |
0.381±0.013 |
0.401±0.016 |
4.987±1.354 |
1.052±0.004 |
|
D14 |
22.67±1.124 |
0.378±0.008 |
0.396±0.004 |
4.545±1.087 |
1.047±0.007 |
|
D15 |
25.22±1.068 |
0.408±0.021 |
0.436±0.012 |
6.422±1.035 |
1.068±0.016 |
*All values are expressed as mean ± SD, n=3.
Table 6: Pre compression evaluation of Doxazosinmesylate powder using effervescent method
|
Formulation Code |
Angle of Repose |
Bulk Density (gm/cc) |
Tapped Density (gm/cc) |
Carr’s Index % |
Hausner Ratio |
|
E1 |
23.29±0.897 |
0.584±0.023 |
0.666±0.039 |
12.281±1.906 |
1.140±0.024 |
|
E2 |
23.86±0.801 |
0.610±0.027 |
0.695±0.035 |
12.292±1.202 |
1.140±0.015 |
|
E3 |
25.58±0.856 |
0.625±0.030 |
0.721±0.028 |
13.307±2.018 |
1.153±0.026 |
|
E4 |
27.69±1.041 |
0.658±0.024 |
0.749±0.031 |
12.203±1.925 |
1.139±0.024 |
|
E5 |
29.62±0.925 |
0.635±0.014 |
0.742±0.011 |
14.427±0.775 |
1.168±0.010 |
*All values are expressed as mean ± SD, n=3.
POST-COMPRESSIONAL PARAMETERS:
All the tablet formulations were evaluated for parameters such as shape, colour, thickness, hardness, friability, weight variation, drug content, in vitro disintegration time, in vitro dispersion time, wetting time, in vitro dissolution studies, model fitting of release profile and stability studies.
a) General appearance:
All the fast dissolving tablets from each batch were found to be flat, white in colour, circular in shape and having good physical appearance. There was no change in the colour and odour of the tablets from all the batches.
b) Thickness:
Thickness of all prepared fast dissolving tablets was measured by using calibrated vernier callipers. Tablet thickness should be controlled within ±0.1% variation of standard value to facilitate packaging and consumer acceptance. The mean thickness was almost uniform in all the formulations and values of tablets prepared by all the methods were ranged from 2.343-2.521 mm. The standard deviation values indicated that all the formulations were within the range.
c) Hardness:
Tablets require certain amount of strength, hardness to withstand mechanical shocks during manufacture, packaging and shipping. The hardness of all the tablets prepared by different methods was maintained within the range of 2.7-3.2 k g /cm2. In all the formulations the hardness test indicates good mechanical strength. In case of sublimation technique the hardness of tablet decreases with increase in amount of sublimable component. The obtained results revealed that the tablets were having good mechanical strength and compactness.
d) Friability:
Adequate tablet hardness and resistance to friability are necessary to prevent damage to the tablet during manufacture, packing and transport. The friability of the formulations was less than 1.0%, showed the durability of the tablets; resistance to loss of weight indicates the tablet’s ability to withstand abrasion in handling, packaging and shipment. The friability was found in all tablet formulations prepared by different methods were well within the approved range (<1%) which indicates the tablets had god mechanical resistance. The friability of all the formulations was found to be less than 1.0 % except those containing higher concentrations of subliming agents (S4, S8 and S12). It was clear from the study that as the concentration of sublimating agents was increasing the percent friability was also increasing.
e) Weight variation:
The average weight of the prepared tablets with superdisintegrants and effervescent agents were found between 95.4-102.1 mg. The average weight of the tablets prepared by vacuum drying technique was found 89.8.3-96.4 mg due to the elimination of the sublimating agents from the tablets. So it was predicted that all the tablets exhibited uniform weight with low standard deviation values within the acceptable variation as per USP.
Mouth feel:
The prepared formulations were subjected for mouth feel. The volunteers felt good taste in all the formulations prepared by both the methods. As the drug is slightly bitter the presence of Aspartame and orange flavour in all the formulations showed good, palatable taste.
PH:
PH of the solution of all the tablets prepared by all the three methods was found to be between 7.1 to 7.5, which suggest that the tablets can be conveniently administered orally and will not cause any discomfort.
f) Drug content:
To evaluate a tablet’s potential for efficacy the amount of drug in the tablet need to be monitored from tablet to tablet and batch to batch. The percentage drug content was found to be in the range of 98.29 to 99.78% for all the tablet formulations prepared by three different methods.
g) Wetting Time:
Wetting time is an important parameter related to water absorption ratio, which needs to be assessed to give an insight to the disintegration properties of the tablets. Wetting is closely related to the inner structure of the tablets and the hydrophilicity of the excipients. Wetting time was used as a parameter to correlate with disintegration time in oral cavity. This is an important criterion for understanding the capacity of disintegrants to swell in presence of little amount of water. Since the dissolution process of a tablet depends upon the wetting followed by disintegration of the tablet, the measurement of wetting time may be used as another confirmative test for the evaluation of dispersible tablets.
The in vitro wetting time was also studied to know the time required for complete wetting of tablets when placed on tongue. The in vitro wetting times of all the formulations were varied between15-112s. The swelling properties of the tablets were depending upon their concentration and type of superdisintegrants. The result shows that swelling time was reduced with increase in the concentration of the superdisintegrant.
As the formulation batches D1 to D15 comprised three different types of superdisintegrants, wetting time was found between 22 and 112 seconds. Hence it was evident that selected superdisintegrants for study played vital role in wetting behaviour. Better wetting time was found with crospovidone and Sodium starch glycolate with respect to batches consisting of Croscarmellose sodium.
Thus wetting time for all these formulation batches varied in the following increasing
Order: Crospovidone> Sodium starch glycolate> Croscarmellose sodium.
Formulation batches S1to S12 comprised of three different types of subliming agents, wetting time was found between 15 and 91 seconds. These batches showed wide variation in their wetting time because of change in not only type but also amount of subliming agents taken for study. In this formulation containing camphor gave better wetting time than rest of three subliming agents.
Formulation batches E1to E5comprised of citric acid and sodium bicarbonate in different concentration, wetting time was found between 20 and 75 seconds.
Table 7: Post compression evaluation of Doxazosin mesylate FDT’s using superdisintegrant addition method
|
Formulation Code |
Thickness (mm)* |
Hardness (kg/cm2)* |
Friability (%)** |
Weight variation test (mg)*** |
Drug Content (%)*** |
pH |
Mouth feel |
|
D1 |
2.436±0.012 |
3.2±0.128 |
0.421±0.069 |
97.1±3.512 |
98.70±0.73 |
7.4 |
+ |
|
D2 |
2.421±0.015 |
3.1±0.133 |
0.484±0.046 |
95.4±3.746 |
98.55±0.09 |
7.5 |
+++ |
|
D3 |
2.414±0.011 |
3.2±0.142 |
0.644±0.073 |
98.2±4.341 |
99.30±0.56 |
7.4 |
++ |
|
D4 |
2.425±0.011 |
3.2±0.123 |
0.765±0.063 |
96.1±3.134 |
99.78±0.28 |
7.2 |
+ |
|
D5 |
2.437±0.009 |
3.1±0.134 |
0.873±0.057 |
98.6±3.561 |
98.65±0.51 |
7.5 |
+++ |
|
D6 |
2.412±0.011 |
3.1±0.122 |
0.412±0.025 |
97.3±2.891 |
98.58±0.44 |
7.2 |
+ |
|
D7 |
2.445±0.008 |
3.1±0.097 |
0.465±0.023 |
96.6±3.140 |
98.29±0.75 |
7.1 |
+++ |
|
D8 |
2.425±0.017 |
3.2±0.124 |
0.526±0.054 |
98.1±2.971 |
98.90±0.65 |
7.1 |
++ |
|
D9 |
2.431±0.014 |
3.1±0.132 |
0.766±0.013 |
102.1±4.12 |
99.47±0.47 |
7.2 |
+++ |
|
D10 |
2.408±0.012 |
3.0±0.116 |
0.923±0.025 |
99.4±3.671 |
99.35±0.53 |
7.5 |
++ |
|
D11 |
2.421±0.018 |
3.0±0.134 |
0.404±0.024 |
98.1±2.982 |
98.85±0.63 |
7.2 |
++ |
|
D12 |
2.396±0.013 |
3.0±0.121 |
0.412±0.017 |
97.5±3.656 |
98.51±0.71 |
7.5 |
++ |
|
D13 |
2.426±0.014 |
3.1±0.143 |
0.456±0.014 |
101.5±4.41 |
97.14±0.72 |
7.2 |
+++ |
|
D14 |
2.401±0.019 |
3.2±0.068 |
0.509±0.053 |
99.4±3.140 |
96.46±0.65 |
7.1 |
++ |
|
D15 |
2.417±0.016 |
3.1±0.089 |
0.584±0.032 |
101.7±2.41 |
96.51±0.74 |
7.3 |
+++ |
*All values are expressed as mean ± SE, n=5; **All values are expressed as mean ± SE, n=10; ***All values are expressed as mean ± SE, n=20; += Average; ++= good, +++= excellent
Table 8: Post compression evaluation of Doxazosin mesylate FDT’s using Sublimation method
|
Formulation Code |
Thickness (mm)* |
Hardness (kg/cm2)* |
Friability (%)** |
Weight variation test (mg)*** |
Drug Content (%)*** |
pH |
Mouth feel |
|
S1 |
2.385±0.014 |
3.1±0.132 |
0.573±0.032 |
96.4±0.128 |
98.70±0.73 |
7.4 |
+ |
|
S2 |
2.409±0.017 |
3.0±0.141 |
0.606±0.037 |
96.1±1.124 |
98.55±0.09 |
7.5 |
+++ |
|
S3 |
2.414±0.009 |
2.9±0.137 |
0.984±0.026 |
92.7±2.317 |
99.30±0.56 |
7.4 |
++ |
|
S4 |
2.426±0.017 |
2.8±0.131 |
1.119±0.021 |
90.4±3.146 |
99.78±0.28 |
7.2 |
+ |
|
S5 |
2.412±0.008 |
3.0±0.213 |
0.576±0.024 |
95.7±0.149 |
98.65±0.51 |
7.5 |
+++ |
|
S6 |
2.396±0.012 |
2.9±0.146 |
0.613±0.054 |
94.2±2.426 |
98.58±0.44 |
7.2 |
+ |
|
S7 |
2.379±0.015 |
2.8±0.135 |
0.997±0.042 |
93.3±0.107 |
98.29±0.75 |
7.1 |
+++ |
|
S8 |
2.371±0.012 |
2.7±0.145 |
1.246±0.027 |
89.8±1.216 |
98.90±0.65 |
7.2 |
+++ |
|
S9 |
2.424±0.009 |
3.1±0.124 |
0.668±0.015 |
95.2±0.141 |
99.47±0.47 |
7.1 |
++ |
|
S10 |
2.417±0.016 |
3.0±0.186 |
0.789±0.019 |
95.3±0.019 |
98.70±0.73 |
7.1 |
++ |
|
S11 |
2.394±0.014 |
2.9±0.136 |
0.969±0.013 |
94.4±1.126 |
98.55±0.09 |
7.2 |
++ |
|
S12 |
2.375±0.011 |
2.7±0.142 |
1.396±0.026 |
90.3±0.219 |
99.30±0.56 |
7.4 |
+++ |
Table 9: Post compression evaluation of Doxazosin mesylate FDT’s using effervescent method
|
Formulation Code |
Thickness (mm)* |
Hardness (kg/cm2)* |
Friability (%)** |
Weight variation test (mg)*** |
Drug Content (%)*** |
pH |
Mouth feel |
|
E1 |
2.344±0.034 |
3.1±0.252 |
0.67±0.143 |
97.9±1.176 |
98.70±0.73 |
7.4 |
+ |
|
E2 |
2.363±0.035 |
3.0±0.276 |
0.78±0.129 |
99.6±3.765 |
98.55±0.09 |
7.5 |
+++ |
|
E3 |
2.343±0.016 |
2.8±0.226 |
0.96±0.159 |
98.4±3.551 |
99.30±0.56 |
7.4 |
++ |
|
E4 |
2.366±0.041 |
2.8±0.234 |
1.19±0.134 |
98.5±3.654 |
99.78±0.28 |
7.2 |
+ |
|
E5 |
2.521±0.339 |
2.7±0.257 |
1.27±0.172 |
100.4±2.246 |
98.65±0.51 |
7.5 |
+++ |
*All values are expressed as mean ± SE, n=5; **All values are expressed as mean ± SE, n=10; ***All values are expressed as mean ± SE, n=20; += Average; ++= good, +++= excellent.
h) Water Absorption Ratio:
Water absorption ratio, which is an important criterion for understanding the capacity of disintegrants to swell in presence of little amount of water, was calculated. The formulations prepared by sublimation technique shows wetting time in the range 18 to 93% and tablets prepared by superdisintegrant method showed wetting time in range of 24 to 115%. Formulations containing camphor (S8) as subliming agent shows lower water absorption ratio when compared to other formulations containing other subliming agents. The lower water absorption ratio due to less swelling property. The Water absorption ratio increased with increase in the concentration of superdisintegrant from 1-5 %. The water absorption ratio was found to be in the increasing order. This increase was due to the water up taking ability of the superdisintegrants. More the superdisintegrant concentration greater was water absorption.
Water absorption ratios for all these formulation batches varied in the following increasing order: Crospovidone> Sodium starch glycolate> Croscarmellose sodium.
Figure5: Comparison of wetting time and Water Absorption Ratio of various formulations of Doxazosin mesylate FDT’s using superdisintegrant addition method
Figure 6: Comparison of wetting time and in vitro disintegration time of various formulations of Doxazosin mesylate FDT’s using sublimation method
Figure 7: Comparison of wetting time and in vitro disintegration time of various formulations of Doxazosin mesylate FDT’s using effervescent method
i) In vitro Disintegration Time:
Disintegration, the first important step for a drug absorption from a solid dosage form after oral administration was preliminarily focused. The internal structure of tablets that is pore size distribution, water penetration into tablets and swelling of disintegration substance are suggested to be the mechanisms of disintegration. This indicates that the tablets would disintegrate almost instantaneously when they will come in contact with even slight amount of saliva in the mouth. Disintegration time was determined as per I.P. for all the formulations. A disintegrant was found in all the formulations to facilitate a breakup or disintegration of the tablet when it contacts with water or saliva in mouth. The disintegration process of the tablet was fully dependable on nature and concentration of superdisintegrant used. Disintegrants drawing the water into the tablet causes wicking, swelling and burst apart. The tablets with crospovidone disintegrate faster than the tablets with the citric acid and sodium-bi-carbonate, sodium starch glycolate and Ac-di-sol and menthol and thymol. The tablets prepared with superdisintegrants disintegrate in27-128 s. The tablets prepared with effervescent technology elaborates the carbon-di-oxide gas when the tablet comes in contact with little amount of saliva or water due to reaction between citric acid and sodium-bi- carbonate which results in breakup of tablets. The tablets prepared with effervescent agents disintegrate in 29-78 s. The porous structure of the tablets prepared with sublimating agents was responsible for the for fast water uptake, which facilitates the disintegration of tablets. The tablets prepared with sublimating agents disintegrate in 25-102s.
The formulations prepared by using various superdisintegrants showed disintegration time less than 25 seconds and the formulation containing various subliming agents showed disintegration time less than 20 seconds. Least in vitro disintegration time was shown by formulation containing crosspovidone (D15), formulation (S8) containing camphor as subliming agent and formulation E5 containing citric acid and sodium bicarbonate(1:2 ratio, 5% conc).
j) In vitro Dispersion Time:
In vitro dispersion time was measured by the time taken to undergo uniform dispersion. All formulations showed rapid dispersion within seconds.
In case of sublimation technique the disintegration time decreased significantly with increase in concentration of subliming agent (camphor, menthol, thymol). The tablets prepared by sublimation technique rapidly exhibit high pores and disintegrate the tablets rapidly. It may be due to their lowest hardness and maximum pours structure was responsible for faster water uptake; hence it facilitates in bringing about faster disintegration. Formulations prepared by sublimation method showed dispersion time in range of 28 sec to99 sec.
In case of disintegrant addition method the disintegration time decreased significantly with increase in concentration of disintegrant (Crospovidone, croscarmellose sodium, sodium starch glycolate). Formulations prepared by superdisintegrants addition method showed dispersion time inrange of 25 sec to125 sec.
In case of effervescent method the disintegration time decreased significantly with increase in concentration of effervescing agent (sodium bicarbonate and citric acid in different conc.). Formulations prepared by effervescent method showed dispersion time in range of 29 sec to78 sec.
Based on the in vitro dispersion time, formulation S8was found to be promising and showed a dispersion time of 20 sec. The results are in consistent with other results.
Figure 8: Comparison between in vitro disintegration time and in vitro dispersion time of various formulations of Doxazosin mesylate FDT’s using effervescent method
Figure 9: Comparison between in vitro disintegration time and in vitro dispersion time of various formulations of Doxazosin mesylate FDT’s using sublimation method
Figure 10: Comparison between in vitro disintegration time and in vitro dispersion time of various formulations of Doxazosin mesylate FDT’s using superdisintegrant addition method
k) In vitro Dissolution Studies:
The in vitro drug release characteristics were studied in phosphate buffer pH 6.8 using tablet dissolution apparatus USP XXIII. The samples were withdrawn at different time intervals and analysed at 245 nm and the cumulative percentage drug released was determined.
As discussed above, differences in the particle size generated in the disintegrated tablets could affect drug dissolution since breaking tablets into finer fragments may promote drug dissolution by providing larger total surface areas for drug dissolution to take place.
The in vitro dissolution studies show that an increase in the drug release was observed when the disintegrant concentration was increased in the formulations. The rapid drug dissolution might be due to easy break down of particles and rapid absorption of drug into the dissolution medium.
As the formulation batches D1 to D15 comprised of three different types of superdisintegrants, in vitro drug release at 10 minutes was found between 76.47 to 100.62 %. Hence it was evident that selected superdisintegrants for study played vital role in dissolution behaviour. Formulation prepared with crospovidone gave the best in vitro drug release than rest of batches consisting of other superdisintegrants.
In tablets prepared by using crospovidone as superdisintegrant showed best dissolution due to more solubility in aqueous medium. When the tablet enters into dissolution medium tablet disintegrate then the drug in molecular form releases due to which the dissolution of tablet increased and drug is released quickly from tablets may be due to their lowest hardness and the porous structure is responsible for faster water uptake.
This is the reason due to which the higher concentration of superdisintegrants in formulation increases the dissolution of tablet.
The formulation batches S1 to S12 comprised of three different types of subliming agents, in vitro drug release at 10 minutes was found between 94.37 to 101.45%. The tablets prepared by sublimation technique rapidly expose high pores and disintegrate the tablets rapidly in dissolution medium. It may be due to their lowest hardness and maximum pours structure was responsible for faster water uptake; hence it facilitates in bringing about faster disintegration. As the concentration of sublimable agent increased the pore structure in the tablet increases. Due to this the formulation containing highest concentration of sublimable agent shows fastest dissolution. The dissolution of the drug from the tablets prepared by camphor as sublimable agent was quicker than other formulations prepared by using other sublimable agents. This may be due to their lowest hardness and the porous structure is responsible for faster water uptake. The formulation batches E1 to E5 comprised of different concentration of sodium bicarbonate and citric acid, in vitro drug release at 10 minutes was found between 89.81 to 99.09%.The tablets prepared with effervescent technology elaborates the carbon-di-oxide gas when the tablet comes in contact with little amount of saliva or water due to reaction between citric acid and sodium-bi- carbonate which results in breakup of tablets. FDTs containing Sodium bicarbonate and citric acid in the ratio of 1:2 (5% conc, E5) shows best results in terms of cumulative percent drug release.
Figure 11: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing crosscarmellose sodium
Figure 12: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing sodium starch glycolate
Figure 13: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing crosspovidone
Figure 14: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing camphor as subliming agent
Table 10: Model fittings of release profile of optimized formulation (S8) Doxazosinmesylate FDT’S using different models
|
FORMULATION CODE |
MATHEMATICAL MODELS (KINETICS) |
|||||
|
Zero Order |
First Order |
Higuchi Matrix |
Peppas |
Hixson Crowell |
Best Fit Model |
|
|
S8 |
0.818 |
0.608 |
0.853 |
1.284 |
0.721 |
Higuchi matrix |
Figure 15: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing menthol as subliming agent
Figure 16: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing thymol as subliming agent
Figure 17: Comparison of dissolution profile of various formulations of Doxazosin mesylate FDT’s containing different Concentration of effervescent agents
Figure 18: Zero order release plot of optimized Doxazosin mesylate FDT S8 batch
Figure 19: Higuchi plot of optimized Doxazosin mesylate FDT S8 batch
Figure 20: Korsmeyer-Peppas plot of optimized Doxazosin mesylate FDT S8 batch
Figure 21: First order release plot of optimized Doxazosinmesylate FDT S8 batch
l) Data Analysis:
The results of in vitro dissolution studies obtained from optimized formulations were plotted in Zero order, First order, Higuchi and Korsmeyer-Peppas release model and Hixson-Crowell equation to study the mechanism of drug release. The formulation S8 showed Higuchi Matrix which described the drug release, as a diffusion process based on the Fick’s law, square root time dependent.
m) Stability Studies:
Stability studies of formulation S8 was performed at 250C ± 20C/60% ±5% RH and 400C ± 20C/75% ± 5% RH for a period up to 60s days. The formulations were selected for stability studies on the basis of their high percentage cumulative drug release and also results of in vitro disintegration time, wetting time and in vitro dispersion studies.
The samples were withdrawn for every 20 days interval and the tablets were analysed for appearance, thickness, hardness, friability, weight variation, drug content uniformity, in vitro disintegration, wetting time and in vitro drug release up to 60 days. The results obtained for physicochemical properties, wetting time, in vitrodisintegration time and in vitro drug release of formulation S8 at250C±20/ 60%±5% RH and 400C ± 20/75% ± 5% RH were shown depicted graphically. There was no change in colour and shape of the tablets when stored at 250C ±20C/60% ± 5% RH and 400C± 20C/75% ±5% RH and observed every 20 days interval up to 60 days. Formulations S8 showed not much variation in any parameter. From these results it was concluded that formulations were stable and retained its original properties.
Figure 22: Wetting time and in vitro disintegration time of formulations S8stored at 250C ± 20C / 60% ± 5% RH
Figure 23: Wetting time and in vitro disintegration time of formulations S8 stored at 400C ± 20C/ 75% ± 5% RH
Figure 24: Cumulative % Drug released from formulation S8 stored at 250C± 20C/60%±5% RH after 60 days
Figure 25: Cumulative % Drug released from formulations S8 stored at 400C ± 20C/ 75% ± 5% RH after 60 day
CONCLUSION:
In this research work ODTs of Doxazosin mesylate were successfully formulated by direct compression method using super disintegration addition method sublimation method and effervescent method.
· FTIR studies concluded that drug and excipients were compatible with each other.
· The flow properties of the formulation powder have good flow property which is an important aspect for the ODT formulations.
· The formulated tablets were satisfactory in terms of hardness, thickness, friability, weight variation, drug content, wetting time, water absorption ratio, in vitro disintegration time, in vitro dispersion time and in vitro drug release.
· The disintegration studies revealed that the tablets prepared with crospovidone, camphor and sodium bicarbonate and citric acid (1:2 ratio, 5 % conc.) as superdisintegrants, subliming agent and effervescent agent respectively showed faster disintegration as compared to tablets prepared with rest of superdisintegrants, subliming agent and other effervescent agent (in different ratio) .
· Dissolution studies confirmed that tablets prepared with crospovidone as disintegrant, camphor as subliming agent and sodium bicarbonate and citric acid (1:2 ratio, 5 % conc.) showed faster drug release as compared to tablets prepared with rest of superdisintegrants, subliming agent and other effervescent agent (in different ratio).
· Direct compression method is the best method for the formulation of ODTs. This method is also very economical and time saving. CP was found to be the best superdisintegrant among all with 5 percent concentration yielding the best results. Similarly camphor was found to be the best subliming agent among all with 8 percent concentration yielding the best results.
· Formulations containing superdisintegrant Crosspovidone and camphor as subliming agent showed least wetting time and in vitro disintegration time.
· Formulation S8 were found to be the best on the basis of wetting time, in vitro disintegration time and in vitro drug release.
· Short term stability studies carried out were confirmative of the drug stability in the tablets during the present study.
ACKNOWLEDGEMENTS:
The authors are thankful to Principal and Management of Karavali College of Pharmacy, Mangalore for providing all the facilities and support for this research project. The authors are also thankful to Aurobindo Pharma Pvt. Ltd. Hyderabad for generous gift samples of Doxazosin mesylate.
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Received on 04.05.2016 Accepted on 04.06.2016
© Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2016; 6(3): 131-146.
DOI: 10.5958/2231-5691.2016.00020.4