Effect of Various Grades of Hydroxypropylmethylcellulose (HPMC) on Drug Release from Naproxen Sodium Matrix Tablets
Kalyani Chithaluru1*, Ramarao Tadikonda2, Chris Vijetha.J1 and K. Kalyan Kumar Kandula3
1Department of Pharmaceutics, K.L.R. Pharmacy College, Khammam, Affiliated to Kakatiya University (K.U)
2Mohammadiya Instititute of Pharmaceutical Sciences, Khammam, Affiliated to K.U
3Actavis Pharma, Bangalore.
*Corresponding Author E-mail: kalyani_josh@yahoo.co.in
ABSTRACT:
The objective of the present study was to design oral sustained release matrix tablets of Naproxen Sodium using different grades of hydroxypropyl methyl cellulose (HPMC) as rate retarding polymer and study the effect of various formulation factors such as polymer proportion and polymer viscosity, effect of different diluents (lactose monohydrate, microcrystalline cellulose), effect of preparation method (direct compression, wet granulation) on the invitro release of naproxen sodium. The release kinetics was analyzed using zero order equation, first order equation, Higuchi’s square root equation and Korsmeyers-peppas equation. FTIR and DSC studies conducted for compatibility revealed that there was no interaction between drug and various excipients used in the study. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. MCC has more retardation of drug release than lactose monohydrate and wet granulation method has more retardation of drug release compared to direct compression. Mathematical analysis of release kinetics indicated the nature of drug release from matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release.
KEYWORDS: Naproxen Sodium matrix tablets, hydroypropyl methyl cellulose, sustained release, influence of formulation variables.
INTRODUCTION:
Oral drug delivery is most widely utilized route of administration among all other routes for systemic delivery of drugs. In the treatment of chronic disease conditions the draw backs of conventional formulations are overcome by sustained release dosage forms. Sustained release dosage forms have advantages of improved patient compliance, reduction in fluctuation in steady state levels, reduction in adverse side effects, improvement in tolerability and increased therapeutic efficiency.
Naproxen Sodium, a non steroidal anti-inflammatory, weakly acidic, crystalline drug has a low aqueous solubility at acidic pH1. It is used in the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrheal, tendonitis, and ankylosing spondalytis and also used as pain reliever and analgesic.
The biological half life of Naproxen Sodium is 15 hrs; it is well absorbed orally and throughout the gastrointestinal tract. The peak plasma levels are attained within 1-2 hrs but due to extensive protein binding (99%), it leads to nonlinear pharmacokinetics, resulting in an increase in urinary excretion of naproxen sodium and its metabolites. Due to these properties it will be more effective to deliver the drug as a sustained release dosage form2.
In all the sustained release dosage forms matrix tablets are very easy to manufacture and cost effective. In formulating matrix tablets for controlling the release of drug, which are having different solubility properties, the drug is dispersed in hydrophilic, hydrophobic or plastic materials .In the formulation of matrix tablets the choice of polymer is very important for controlling the release. Sustained release can be achieved by using various hydrophilic polymers like cellulose ethers3, HPMC4, sodium CMC and hydrophobic polymers like ethyl cellulose5, acrylic polymers6. Hydrophilic polymers are very particular interest in sustained release dosage forms especially HPMC. The major advantage of HPMC is the non-ionic nature, cost effective, broad FDA acceptance, vast range of viscosities, desirable drug release and wide pH range.
Hence, the present study was aimed to formulate sustained-release matrix tablets of Naproxen sodium (275 mg) using different grades of hydrophilic HPMC polymers like HPMC K100LV, K4M, K15M, K100M and Metolose 90SH in different proportions.
The formulation variables also influence the release of drug. In this study also work on effect of formulation variables like nature of diluents (MCC and lactose monohydrate) and effect of preparation method (wet granulation, direct compression).
MATERIALS AND METHODS:
Materials:
Naproxen Sodium was a kind gift from Divis Laboratories Pvt Ltd, Hyderabad. Hydroxypropyl methyl cellulose (HPMC) K100LV, K4M, K15M, K100M and Metolose 90SH were kind gift from Colorcon India Pvt Ltd, Mumbai, Microcrystalline cellulose (MCC) was from Lupin Laboratories, Pune. All other chemicals or ingredients used in this study are either analytical or pharmaceutical grade.
Methods:
Preparation of Matrix Tablets by wet granulation:
The matrix tablets of Naproxen sodium were prepared by wet granulation method. Naproxen Sodium was dry blended with appropriate quantity of polymer HPMC and diluent MCC and granulated using 5% w/v of starch paste. The wet mass was passed through a no.16 sieve. The wet granules were dried at 55oC ± 5oC for half an hour and sieved through no.20 sieve. The drug granule mixture was blended with 1% magnesium stearate and 2% talc and mixed for 5 minutes. This granule mixture was compressed using 16 station rotary tableting machine (Cadmach Machinery Co, Ahemdabad) equipped with round, concave faced punches of 12.5mm diameter. The drug and polymer ratio was varied to get matrix tablets of varying polymer concentrations. (table-1)
Preparation of matrix tablets by direct compression:
Accurately weighed amount of drug polymer and diluent were mixed geometrically in a mortar. This mixture was passed through No.40 sieve and thoroughly mixed in a polyethylene bag for 15 minutes. The powder blend was then pre lubricated with talc and lubricated with magnesium stearate. The lubricated blend was compressed on 16 station rotary punching machine equipped with round, concave faced punches of 12.5mm diameter.
Characterization of granules:
Granulation is the key process in the production of many dosage forms involving the controlled release of a drug from matrix from coated or matrix particles. Prior to compression granules were evaluated for their characteristic parameters such as angle of repose, loose bulk density (LBD), tapped bulk density (TBD) and carr’s index.
Physical Evaluation of Matrix Tablets:
Formulated tablets were evaluated for certain physicochemical properties like hardness7, thickness8, friability, weight variation8 and in vitro drug release and drug content. Tablet diameter and thickness were determined by using digital vernier calipers. Hardness was determined by Monsanto type hardness tester. By Roche friabilator (Campbell Electronics, Mumbai, India) friability was measured8. All the tablets should be uniform in weight and the weight variation should be within the limits8. Weights were determined by using digital weigh balance (Shimadzu) within±1mg. For determination of drug content 6 tablets were crushed and powder equivalent to one tablet weight (500mg) was transferred into 100ml volumetric flask containing 60ml of 7.4 pH phosphate buffer and sonicated for half an hour. After the solution was made up to the mark with 7.4 phosphate buffer. From this solution 1mL was taken, diluted to 50ml with 7.4 phosphate buffer and absorbance was measured against blank at 330nm using UV-Visible double beam (Elico 161, Hyderabad) spectrophotometer.
In Vitro dissolution studies were performed for prepared naproxen sodium tablets over a period of 12 hrs using USP type II (Electro lab, TDT-08L) dissolution test apparatus (paddle method) at 50 rpm in 900 mL of pH 7.4 phosphate buffer maintained at 37°C ± 0.5°C. An aliquot of (5mL) was withdrawn at specified time intervals and replaced with the same volume of fresh dissolution medium. The samples withdrawn were filtered through Whatman filter paper (No.1) and drug content in each sample was analyzed by UV-Visible spectrophotometer at 330 nm.
Kinetic Analysis of Dissolution Data:
To analyze the in vitro release data various kinetic models were used to describe the release kinetics. The zero order rate Eq. (1) describes the systems where the drug release rate is independent of its concentration9. The first order Eq. (2) describes the release from system where release rate is concentration dependent10. Higuchi11 (1963) described the release of drugs from insoluble matrix as a square root of time dependent process based on Fickian diffusion Eq. (3).
C=K0t ----------------------------------------------------------- (1)
K0 is zero-order rate constant expressed in units of concentration/time and t is the time.
LogC=LogC0-K1t/2.303 -------------------------------------- (2)
Where, C0 is the initial concentration of drug and K1 is first order constant.
Q=KHt1/2 -------------------------------------------------------- (3)
Where, KH is the constant reflecting the design variables of the system.
The following plots were made using the in-vitro drug release data
Cumulative % drug release vs. time (Zero order kinetic model);
Log cumulative of % drug remaining vs. time (First order kinetic model);
Cumulative % drug release vs. square root of time (Higuchi model)
For mechanism of drug release Korsmeyer et al (1983)12,13 derived a simple relationship which described by Eq. (4).
Mt/M∞=Ktn ----------------------------------------------------- (4)
where Mt / M∞ is fraction of drug released at time t, K is the release rate constant incorporating structural and geometric characteristics of the tablet, and n is the release exponent. The n value is used to characterize different release mechanisms.
A plot of log cumulative % drug release vs. log time(Korsmeyer peppas model)
Diffusion exponent (n) |
Overall solute diffusion mechanism |
0.45 |
Fickian diffusion |
0.45 < n < 0.89 |
Anomalous (non-Fickian) diffusion |
0.89 |
Case-II transport(Zero Order ) |
n > 0.89 |
Super case-II transport |
Determination of compatibility of the drug with used excipients done by FTIR (Fourier transform infrared spectroscopy). FTIR was done for pure naproxen sodium and optimized formulation. About 2-3mg of samples were mixed with dried IR grade potassium bromide powder and analyzed by FTIR spectrophotometer (Thermo nicolet 670 spectrometer) in the frequency range between 400 to 4000cm-1
RESULTS AND DISCUSSION:
Characterization of granules:
The physical properties of granules (Angle of repose, loose bulk density, tapped bulk density and compressibility index) are shown in Table-2. The results of angle of repose and compressibility index (%) ranged from 20.33±0.22 to 29.25±0.76 and 9.74 + 0.91to 15.90±0.26 respectively. The results of angle of repose (<30) indicates good flow properties to the granules and this was further supported by lower compressibility (up to 15%) index values. The results of LBD and TBD ranged from 0.214±0.64 to0.481±0.78 and 0.251±0.68 to 0.388±0.87 respectively.
Physical Evaluation of Matrix Tablets:
The thickness of the tablets ranged from 2.98±0.88 to 3.42±0.89. The average percentage deviation of 20 tablets of each formula was less than ±5%. In a weight variation test, the pharmacopoeial limit for the % deviation for the tablets of more than 250mg is ±5%. Drug content was found to be uniform among different batches of the tablets and ranged from 96.34±2.18 to 101.2±0.89. The hardness and % friability of the tablets of all batches ranged from 4.6±0.84 to 6.2±0.57 and 0.36±0.08 to 0.77±0.13 (Table-3) respectively. Tablet hardness is not an absolute indicator of strength another measure of tablet's strength is friability. In the present study, the percentage friability for all the formulations was below 1%, indicating that the friability is within the prescribed limits. All the tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for weight variation, drug content, hardness and friability.
In Vitro Dissolution studies:
The results of dissolution studies of formulations containing F1, F2 composed of low viscosity grade of HPMC such as HPMC K100LV at different concentrations (10%, 20%).The invitro dissolution study clearly reveals there is rapid drug release from matrix tablets. The drug was completely disintegrated in the 3hrs in all the formulations. The results of UV analysis showed 100% drug release occurs in 3 hrs from both formulations. This clearly indicates HPMC K100LV at 10% and 20% are insufficient to retard the drug release or not suitable for sustained release. Further increase in concentration of HPMC K100LV did not significantly affect the release rate.
The results of dissolution studies of formulations containing F3, F4 and F5 composed of HPMC K4M polymer at different concentrations (10%, 15% and 20% respectively) are shown in Fig.1. From F3, F4 (10%, 15 % of K4M) 98.24%, 98% of drug release occurs within 4hrs, 5hrs respectively. Faster drug release may be due to faster dissolution of the water soluble drug from matrix tablets. From F5 98.94% drug release observed for 6hrs.Increasing polymer concentration cause increasing gel viscosity and retardation of drug occurs up to 6hrs. HPMC K4M up to 20% concentration also insufficient to retard the drug release from matrix tablets.
Fig 1: Cumulative % drug Release from HPMC K4M Matrix Tablets
The results of dissolution studies of formulations F6, F7 and F8 composed of HPMC K15M polymer at different concentrations are shown in Fig 2. Formulation F6 releases 98% of drug with in 8hrs.Rapid drug release Formulations F7, F8 releases 97.12%, 88.56% naproxen sodium for 12 hrs respectively. In F8 contains higher amount of polymer showed slower drug release14. From the results indicates the drug release not only dependent on the nature of the polymer but also drug polymer ratio.
Fig 2: % Drug Release from HPMC K15M Matrix Tablets
Table-1.Composition of Naproxen sodium (275mg) matrix tablets
F. Code |
HPMC K100LV |
HPMCK4M |
HPMCK15M |
HPMCK100M |
Meto lose 90SH |
MCC (200) |
Lactose monohydrate |
F1 |
50 |
- |
- |
- |
- |
135 |
- |
F2 |
100 |
- |
- |
- |
- |
85 |
- |
F3 |
- |
50 |
- |
- |
- |
135 |
- |
F4 |
- |
75 |
- |
- |
- |
110 |
- |
F5 |
- |
100 |
- |
- |
- |
85 |
- |
F6 |
- |
- |
50 |
- |
- |
135 |
- |
F7 |
- |
- |
75 |
- |
- |
110 |
- |
F8 |
- |
- |
100 |
- |
- |
85 |
- |
F9 |
- |
- |
- |
50 |
- |
135 |
- |
F10 |
- |
|
- |
75 |
- |
110 |
- |
F11 |
- |
- |
- |
100 |
- |
85 |
- |
F12 |
- |
- |
- |
- |
50 |
135 |
- |
F13 |
- |
- |
|
- |
75 |
110 |
- |
F14 |
- |
- |
- |
- |
100 |
85 |
- |
F15 |
- |
- |
75 |
- |
- |
- |
110 |
MCC-Microcrystalline cellulose, DCP- Dicalcium phosphate
All the formulations had 5% starch as a binder, talc 2% as glidant and magnesium stearate 1% as a lubricant. Total weight of the tablet is 500mg
Table-2.Physicochemical properties of matrix granules
F. Code |
Angle of repose ( °) |
Bulk density (g/mL) |
Tapped Density (g/mL) |
Carr’s Index (%) |
F1 |
25.49±0.32 |
0.214±0.64 |
0.251±0.68 |
14.74±0.77 |
F2 |
26.24±0.43 |
0.308±0.89 |
0.364±0.73 |
15.38±0.59 |
F3 |
29.05±0.55 |
0.276±0.55 |
0.322±0.69 |
14.28±0.88 |
F4 |
26.97±0.33 |
0.341±0.75 |
0.388±0.87 |
12.11±1.29 |
F5 |
29.25±0.76 |
0.324±0.55 |
0.376±0.95 |
13.82±0.99 |
F6 |
22.27±0.58 |
0.253±0.22 |
0.278+0.65 |
14.37+0.67 |
F7 |
22.64±0.49 |
0.240+0.35 |
0.269+0.25 |
9.74 + 0.91 |
F8 |
21.21±0.66 |
0.242+0.07 |
0.272+0.47 |
11.6 + 0.92 |
F9 |
26.56±0.43 |
0.264+0.28 |
0.307+0.21 |
15.33+2.96 |
F10 |
20.33±0.33 |
0.481±0.78 |
0.572±0.75 |
15.90±0.26 |
F11 |
27.33±0.86 |
0.259+0.42 |
0.268+0.19 |
12.33+2.87 |
F12 |
25.38±0.73 |
0.240+0.54 |
0.262+0.13 |
14.86+1.19 |
F13 |
27.53+0.48 |
0.245+0.24 |
0.279+0.22 |
14.7 + 0.85 |
F14 |
26.17+1.73 |
0.234+0.22 |
0.265+0.28 |
12.60+ 2.8 |
F15 |
25.36+0.57 |
0.242+0.07 |
0.270+0.24 |
13.01 + 2.1 |
All values represent mean ± SD, n = 3
Table-3.Physical Evaluation of Naproxen sodium Matrix Tablets
F. Code |
Hardness (kg/cm2 † |
Thickness (mm) ‡ |
Weight Variation (mg) (%) ‡ |
Friability (%)‡ |
Drug content * (%) |
F1 |
5.5±0.44 |
3.22±0.17 |
497.8±1.48 |
0.36±0.08 |
98.25±1.37 |
F2 |
5.3±0.31 |
3.24±0.71 |
498.6±0.41 |
0.39±0.05 |
98.28±0.80 |
F3 |
5.8±0.40 |
3.38±0.73 |
497.8±1.64 |
0.43±0.13 |
99.12±2.47 |
F4 |
5.6±0.55 |
3.32±0.89 |
500.6±1.14 |
0.52±0.15 |
101.22±0.88 |
F5 |
5.2±0.57 |
3.00±0.68 |
499.2±0.83 |
0.54±0.06 |
100.24±1.25 |
F6 |
6.1±0.30 |
2.98±0.88 |
499.9±0.67 |
0.58±0.17 |
99.53±1.87 |
F7 |
6.2±0.57 |
3.33±0.25 |
498.0±0.43 |
0.64±0.15 |
99.28±1.99 |
F8 |
5.4±0.60 |
3.08±0.66 |
500.0±0.80 |
0.37±0.09 |
97.35±1.14 |
F9 |
6.0±0.44 |
3.20±0.20 |
499.2±0.83 |
0.48±0.07 |
98.35±1.14 |
F10 |
5.0±0.31 |
3.14±0.80 |
498.1±0.93 |
0.77±0.13 |
96.34±2.18 |
F11 |
5.0±0.37 |
3.37±0.25 |
499.2±0.97 |
0.42±0.07 |
99.29±0.98 |
F12 |
5.4±0.70 |
3.22±0.17 |
498.4±0.87 |
0.56±0.98 |
97.35±0.43 |
F13 |
5.2±0.78 |
3.11±0.36 |
502.4±0.45 |
0.34±0.87 |
98.88±0.88 |
F14 |
5.5±0.98 |
3.22±0.78 |
504.4±0.67 |
0.45±0.14 |
101.2±0.98 |
F15 |
4.9±0.77 |
3.42±0.89 |
502.4±0.57 |
0.37±0.56 |
100.2±0.89 |
* † All values represent mean ± SD, n = 6, ‡ All values represent mean ± SD, n = 20
The results of release studies of formulations F9 to F11 composed of HPMC K100M (10%, 15% and 20% respectively) are shown Figure 3. The matrix tablets of Naproxen Sodium F9, F10 and F11 releases about 66.75%, 55.24% and 41.24% respectively in 12 hrs testing intervals. As the amount of HPMC polymer increased a significant decrease in the rate and extent of drug release due to matrix hydration controlled by high molecular weight HPMC.
The results of dissolution studies of formulations F12, F13 and F14 composed of Metolose 90SH S polymer at different concentrations are shown in Fig 4. Formulations F12, F13 and F14 releases about 35.25%, 30.25% and 26.78% respectively in 12hrs testing intervals. Metolose 90SH is higher viscosity (2,00,00 MW) grade of HPMC. The slower drug release in higher viscosity grade polymer is increased tortuosity (or) gel strength of the polymer. These dehydrated hydrogels after absorption of water results hydration and swelling. Higher viscosity grades of HPMC when exposed to aqueous medium hydration is fast but delayed chain relaxation leads to formation of viscous gelatinous layer and more drug retardation occurs from matrix tablets. By observing the dissolution profiles HPMC K15M at 15% polymer concentration (F7) the optimum drug release was observed.
Fig 3: % Drug Release from HPMC K100M Matrix Tablets
Fig 4: Cumulative % drug Release from Metolose 90SH Matrix Tablets
Kinetic analysis of dissolution data
In vitro dissolution profiles were fitted into zero order, first order and higuchi for determination of order of drug release. The regression coefficients of values of the various models of all formulations are presented in Table 4. From the regression coefficients the in vitro drug release of naproxen sodium matrix tablets were best explained by higuchi’s equation as the plots showed the highest linearity (r2 =0.9744 to 0.9965) followed by zero order(r2 =0. 8998 to 0.983)followed by first order(r2 =0.86872 to 0.9897).
Determination of drug release the dissolution data was fitted into korsmeyer-peppas equation and the formulations showed highest linearity (r2 = 0.9734 to 0.9968). The release exponent ‘n’ values ranged from (n = 0. 46 to 0.65) indicating that the release mechanism is non-Fickian or anomalous diffusion mechanism (0.45 < n < 0.89)15. It can be interfered that the release was dependent on both drug diffusion and polymer relaxation. The drug release was controlled by more than one process.
Effect of Viscosity of HPMC on Drug Release:
The effect of HPMC viscosity on the drug release from formulations containing same proportion of the polymer (20% of HPMC) is showed in Fig.5 As the viscosity of HPMC increased from100cps (K100LV) to 2,00,00 (Metolose 90SH), the release rate was retarded from 2 hrs to more than 24 hrs. The values of K(first order rate constant) decreased from 0.856hr-1 to 0.025 hr-1 and the values of t1/2 (Biological half life) increased from 0.81hrs to 27.1hrs . This observation was in agreement with the other reported works16 .Rapid release of drug from lower viscosity grade polymer is due to less polymer entanglement and poor gel strength compared to high viscosity grade polymers. Increasing polymer viscosity, rate of swelling increased and automatically the erosion was decreased. Percentage of swelling and erosion was completely dependent on the viscosity of the polymer. Lower viscosity grade polymer have lower absorption capacities and swelling is slow but high viscosity grades have higher and faster absorption capacities leads to more gel strength and less erosion17,18. For these reasons diffusional path length increased and the diffusion coefficient of the drug through the matrix decreased as the viscosity of HPMC increased from 100 cps to 2,00,000 cps. The amount of drug release from various matrix tablets was found to be in the order of HPMC K100LV> HPMCK4M> HPMCK15M> HPMCK100M>Metolose 90SH.
Fig.5.Effective of HPMC viscosity(20%) on % of drug release
Effect of diluents and method of preparation on drug release:
The influence of nature of the diluents and method of preparation studies HPMC K15M (15%) was selected because in that formulation 97.12% drug release occurs 12hrs. Fig. 6 shows comparative dissolution profiles of 15% HPMC K15M polymer using MCC and Lactose (F7, F15) diluents respectively. Significant divergence was observed in the drug release. F7 releases 97.12% for 12hrs but F15 releases total amount of the drug with in 6hrs.The difference is in dissolution profiles is due to the difference in the solubility and subsequent tortuosity factor. Lactose showed greatest release because it is water soluble filler; it dissolves easily by penetrating the dissolution medium into the matrix tablet and tortuosity decreases and rapid drug release occurs. This was not occurring in MCC but it swells in water, produces a porous network within the matrix tablet19.
Table 4. Correlation coefficient (R2), first order rate constant, half life and release exponent (n) values for different kinetic models
F. Code |
Zero order |
First Order |
First order rate constant |
t1/2 |
Higuchi’s |
Korsmeyer |
Peppas ’n’ |
F3 |
0.7833 |
0.9897 |
0.856 |
0.81 |
0.9745 |
0.9968 |
0.46 |
F4 |
0.8681 |
0.8687 |
0.655 |
1.05 |
0.9806 |
0.9734 |
0.47 |
F5 |
0.8771 |
0.8968 |
0.444 |
1.55 |
0.9826 |
0.975 |
0.46 |
F6 |
0.9804 |
0.9499 |
0.283 |
2.44 |
0.9522 |
0.987 |
0.57 |
F7 |
0.9625 |
0.9287 |
0.226 |
3.21 |
0.9875 |
0.9848 |
0.47 |
F8 |
0.9221 |
0.9761 |
0.162 |
4.28 |
0.9934 |
0.9797 |
0.65 |
F9 |
0.9588 |
0.9855 |
0.089 |
7.76 |
0.9744 |
0.9863 |
0.52 |
F10 |
0.873 |
0.9862 |
0.061 |
11.9 |
0.9822 |
0.9823 |
0.51 |
F11 |
0.9464 |
0.9723 |
0.042 |
16.1 |
0.9912 |
0.9926 |
0.55 |
F12 |
0.9527 |
0.9722 |
0.034 |
19.9 |
0.9876 |
0.9949 |
0.60 |
F13 |
0.9427 |
0.9607 |
0.029 |
23.2 |
0.9872 |
0.9939 |
0.62 |
F14 |
0.9242 |
0.9423 |
0.025 |
27.1 |
0.9862 |
0.9872 |
0.65 |
F15 |
0.9177 |
0.9529 |
0.393 |
1.76 |
0.9965 |
0.9429 |
0.63 |
Fig.6.Effect of diluent on drug release
Selection of proper granulation is necessary for sustained release matrix tablets. The process of the tablets preparation directly effect on the physicochemical properties of the tablets such as invitro dissolution and sometimes directly shows in-vivo performance. Fig.7 showed dissolution profiles F7 formulation by direct compression and wet granulation method (starch paste). In wet granulation more retardation drug occurs compared to the direct compression.
Fig.7.Effectof method of preparation on drug release
Drug-excipient interaction:
Fig.8 shows FTIR spectra of pure naproxen sodium(A),optimized formulation(F7) containing HPMC K15M with MCC as diluent(B), F15 containing HPMC K15M with lactose as diluent(C). Pure naproxen sodium exhibits sharp bands at Naproxen Sodium exhibits sharp bands at 1213 C due to C-O stretching(ether), 1258 cm-1 due to C-O stretching(acid), 1397 cm-1 to 1363 cm-1 due to CH3 bending, 3373 cm-1 due to aromatic stretching, 2940 cm-1 and 2930 cm-1 due to aliphatic stretching and at 3057 cm-1 and 2838 cm-1 due to C-H aliphatic stretch. The remaining FTIR spectrums also showed similar peaks at the above wave numbers. It reveals there is no drug excipient interaction.
Fig.8 shows FTIR spectra of pure naproxen sodium(A),optimized formulation(F7) containing HPMC K15M with MCC as diluent(B), F15 containing HPMC K15M with lactose as diluent(C)
CONCLUSION:
Hydrophilic matrix tablets of Naproxen Sodium with different grades of HPMC were developed could improve patient compliance and quality of life. The results of this study enable us to state that different viscosity grades, nature of the diluent and method of preparation will influences the drug release.
ACKNOWLEDGEMENT:
The authors are grateful Divis Laboratories Pvt. Ltd., Hyderabad, India, Colorcon India Pvt. Ltd., Mumbai, India for generous gift samples of naproxen sodium and Hydroxypropyl methyl cellulose (HPMC) K100LV, K4M, K15M, K100M and Metolose 90SH respectively.
REFERENCES:
1. Kiran S. Bhise, Ravindra S. Dhumal, Anant R. Paradkar, and Shivajirao S Kadam, Effect of drying methods on swelling, erosion and drug release from chitosan-naproxen sodium complexes, AAPS PharmSci Tech, Vol 9, No. 1, (2008); DOI 10: 1208/S 12249-007-9001-0.
2. S. Mahesh Kumar, M. J. N. Chandrasekhar, R. Gopinath, R. Srinivasan, M. J. Nanjan and B. Suresh, In vitro and in vivo studies on HPMC K100M matrices containing naproxen sodium. Drug Delivery. (2007) 14:163-169; DOI 10:1080/10717540601098682.
3. Vueba ML, Batista de Carvalho LA, Veiga F, Sousa JJ, Pina ME. Role of cellulose ether polymers on ibuprofen release from matrix tablets. Drug Develop Ind Pharm, 2005; 31: 653-665.
4. Vueba ML, Batista de Carvalho LA, Veiga F, Sousa JJ, Pina ME. Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets. Eur J Pharma Biopharma. 2004; 58(1):51-59.
5. Kuksal A, Tiwary A K, Jain, N K, Jain S. Formulation and in vitro, in vivo evaluation of extended release matrix tablet of zidovudine: influenceof Combination of hydrophilic and hydrophobic Matrix Formers. AAPS. PharmSciTech, 2006; 1: 1-9.
6. Mehta KA, Kislaloglu MS, Phuapradit W, Malick AW, Shah NH. Release performance of a poorly soluble drug from a novel Eudragit-based multiunite erosion matrix. Int J Pharm, 2001; 213: 7–127. Banker GS, Anderson NR. Tablets. In: Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 3rd ed. Philadelphia: PA: Lea& Febiger; 1986; 293-45.7.
7. Banker GS, Anderson NR. Tablets. In:Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 3rd ed. Philadelphia: PA: Lea& Febiger; 1986; 293-45.
8. Martin A, Micromeritics, In: Physical Pharmacy. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001; 423-52.
9. T.P. Hadjiioannou, G.D. Christian, M.A. Koupparis, Quantitative Calculations in Pharmaceutical Practice and Research, VCH Publishers Inc, New York, NY. (1993) pp. 345-348.
10. D.W. Bourne, Pharmacokinetics, In: G.S. Banker, C.T. Rhodes, eds, Modern Pharmaceutics, 4th ed, New York, NY; Marcel Dekker Inc (2002) 67-92.
11. T. Higuchi, Mechanism of sustained action medication, theoretical analysis of rate of release of solid drugs dispersed in solid matrices, J Pharm Sci. 52 (1963) 1145-1149.
12. R.W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, N.A. Peppa, Mechanisms of solute release from porous hydrophilic polymers, Int J Pharm. 15 (1983) 25-35.
13. N.A. Peppas, Analysis of fickian and non-fickian drug release from polymers, Pharm Acta Helv. 60 (1985) 110-111.
14. N.K. Edube, A.H. Hikal, M.W. Christy, A.B. Jones, Effect of drug formulation process variables on granulation and compaction characteristics of heterogeneous matrix, Int J Pharm. 156 (1997) 49-57.
15. E. Jaber, and T. Naser, Formulation of sustained-release lithium carbonate matrix tablets: influence of hydrophilic materials on the release rate and in vitro-in vivo evaluation, J Pharm Pharmaceut Sci. 7(3) (2004) 338-344
16. H. Kim, R. Fassihi, Application of binary polymer system in drug release rate modulation, 2: influence of formulation variables and hydrodynamic conditions on release kinetics, J Pharm Sci. 86 (1997) 323-328
17. S.C. Basak, B.M. Jayakumar Reddy, K.P. Lucas Mani, Formulation and release behaviour of sustained release ambroxol hydrochloride HPMC matrix tablet, Indian J Pharm Sci. (2006) 594-597.
18. R.A. Fassihi and W.A. Ritschel, Multiple layer direct compression controlled release system: invitro and invivo evaluation, J Pharm Sci 82 (1993) 750-754.
19. Silvina AB, Maria CL, Claudio JS. In-vitro studies of diclofenac sodium controlled release from biopolymeric hydrophilic matrices. J Pharm Pharmaceut. Sci.2002:5(3):213-219.
Received on 13.08.2010 Modified on 01.09.2010
Accepted on 11.09.2010 © RJPT All right reserved
Research J. Pharm. and Tech. 4(2): February 2011; Page 223-229