Formulation and Comparative Evaluation of Etoricoxib Loaded Osmotic Drug Delivery Systems

 

Muthukumar S¹*, Sankar C¹, Arul kumaran G¹, Shalini S², Vinesha R¹, Shalumol Varghese¹

¹Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India.

(Affiliated to The Tamil Nadu Dr. M.G.R. Medical University, Chennai )

²Department of Pharmacy Practice, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India.

(Affiliated to The Tamil Nadu Dr. M.G.R. Medical University, Chennai)

 

ABSTRACT:

Osmotic drug delivery systems are gaining interest as they deliver the drug based on the principle of osmosis. Osmosis is defined as the spontaneous movement of solvent from a solution of lower solute concentration to a solution of higher solute concentration through a semipermeable membrane Aim of this study was to formulate and evaluate oral osmotic drug delivery systems of Etoricoxib for the treatment of inflammation and arthritis. A single compartment system (tablet) and a multi-compartment system (capsule) have been prepared. The granules for the osmotic tablet were prepared by wet granulation technique using PVP K 30 in ethanol as binder. The granules were evaluated for its flow property and the tablets were compressed and coated. Then the osmotic capsules of Etoricoxib was prepared and coated. A micro orifice was drilled for the capsule. Both the tablets and capsules were evaluated and the best formulation was determined. The release studies showed that F1 formulation (osmotic tablet) which contained equal proportion of mannitol and lactose as osmogens showed a maximum release of 68.56% and was the most promising among the 6 formulations. The kinetic analysis was done for F1. The formulation was found to be stable at an accelerated temperature of 40° ± 2°C, RH 70 % ± 5 % for 45 days.

 

 

 

INTRODUCTION:

For the past years, many therapeutically active molecules have been developed for the prevention and treatment of diseases. Even though pharmacological activity of these molecules is the primary requirement, it is also important that the molecule reaches the site of action in the right dose and at right time. Therefore, the formulators are developing new dosage forms for the appropriate delivery of the developed molecules to the site of action¹. Scientists are doing frequent researches on the development of new molecules which have good absorption and pharmacokinetic properties. Many of the existing molecules have poor pharmacokinetic properties such as less absorption, short biological half-life, gastrointestinal degradation².

 

Conventional dosage forms give instantaneous release of the drug, and hence it cannot give a prolonged action. The release from these dosage forms depends on the GI pH, presence of food, GI motility, etc³. Moreover, many conventional dosage forms need frequent dosing which leads to patient intolerance and side effects⁴. Controlled release dosage forms, transdermal patches, implants, etc can be used in overcoming these problems. Although the cost of developing these dosage forms is more, it is less when compared to the cost for developing a new molecule². Many conventional dosage forms have been developed by formulators. But most of them had drawbacks. So, the phenomenon of osmosis can be used to reduce many such drawbacks⁵. Osmotic drug delivery system comes under the category of controlled release drug delivery systems, in particular, physical means of activation modulated drug delivery system⁶. Controlled drug delivery system is classified as Rate-preprogramed drug delivery systems, Activation-modulated drug delivery systems, Feedback-regulated drug delivery systems, Site targeting drug delivery systems. Osmotic pressure-activated drug delivery systems are physical means under the type activation-modulated drug delivery systems

 

OSMOTIC DRUG DELIVERY SYSTEMS:

Osmosis is defined as the spontaneous movement of solvent from a solution of lower solute concentration to a solution of higher solute concentration through a semi-permeable membrane. This membrane is permeable only to solvent but impermeable to solute. The pressure which is applied to the higher concentration side to inhibit solvent flow is called osmotic pressure. The first osmotic effect was reported by Abbe Nollet in 1748. Later, Pfeffer performed an experiment on osmosis in 1877. The experiment was to separate sugar solution from pure water, using a semi-permeable membrane. He proved that the osmotic pressure of sugar solution is directly proportional to the concentration of the solution and absolute temperature. In 1866, Van Hoff gave the relationship between concentration, temperature and osmotic pressure. The equation was as follows: π=n2RT (1) Where, π is the osmotic coefficient, n2 is the molar concentration of solute in the solution, R is the gas constant, T is the absolute temperature.

 

Osmotic pressure is a colligative property. The osmotic pressure exhibited by a solution is directly proportional to its concentration. Thus, a constant osmotic pressure followed by a constant influx of water can be achieved using an osmotic drug delivery system, which results in zero order release of the drug. The release of drug from osmotic systems depends on the solubility of the drug and also on osmotic pressure of the core. So, these systems can be used for the delivery of moderately water-soluble drugs⁵. Drugs used in osmotic pumps are generally potent and those used for prolonged therapy. Magnesium sulphate, sodium chloride, sodium sulphate, potassium chloride and sodium bicarbonate are some of inorganic osmogens. Sodium carboxy methyl cellulose, hydroxyl cellulose, methyl cellulose, cellulose (cross linked), polyvinyl pyrollidone and poly polyethylene oxide are important organic polymeric osmogens⁷. Osmotic pumps consist of an osmogen, a solvent and the active drug. So, the osmotic pumps can be categorized into three: single compartment pumps, two compartment pumps, multi-compartment systems. Single and two compartment pumps are driven by water from body fluids while multi-compartment systems have an additional compartment containing water, separated from the osmogen by a semipermeable membrane e.g.: as a part of extracorporeal systems⁸

 

The advantages of osmotic drug delivery system are numerous: it is possible to achieve zero-order release with osmotic systems. It is possible to delay the delivery, if required. The release rates from osmotic systems are predictable and can be altered easily by adjusting the parameters. Drug release from osmotic systems is independent of GI pH and hydrodynamic conditions. Presence of food will not affect the release of the drug. A high degree of in vitro- in vivo correlation is obtained with osmotic systems. Higher release rate of the drug is possible with osmotic systems when compared to conventional drug delivery systems.

 

The limitations faced in osmotic drug delivery system ^3,5,9 include: Chances of dose dumping. Chances of rapid development of tolerance. Retrieval of therapy is not possible in case of unexpected side effects. Expensive than conventional dosage form. The size of the orifice is critical. So, special equipment needed for making the orifice. If the coating is not proper, there are chances of dose dumping. Chances of gastric irritation due to the release of saturated solution. systems⁷. The basic components of osmotic systems^{3,10,11,12,13,14} are: drugs which have short biological half-life and which are used for prolonged treatment are ideal candidates for osmotic systems. Diltiazem hydrochloride, Carbamazepine, Metoprolol, Oxprenolol, Nifedipine, Glipizide, etc are formulated as osmotic delivery. Osmotic agents are used to maintain a concentration gradient across the membrane. They generate a driving force for the uptake of water and assist in maintaining drug uniformity in the hydrated formulation. Different types of osmogens which can be used are sodium chloride, potassium chloride, mannitol, lactose. Hydrophilic and hydrophobic polymers are used in the formulation of osmotic systems for making drug containing matrix core. The polymer selection is based on the solubility of the drug as well as the amount and rate of drug to be released from the pump. The polymers may be either swellable or non-swellable in nature. Mostly, swellable polymers are used for the pumps containing moderately water-soluble drugs, since they increase the hydrostatic pressure inside the pump due to their swelling nature. The non-swellable polymers are used in case of highly water-soluble drugs. E.g.: HPMC, ethyl cellulose, carboxy methyl cellulose Delivery systems can be formulated to regulate the permeability of the fluid by incorporating flux-regulating agents in the layer. Hydrophilic substances improve the flux, whereas hydrophobic materials tend to decrease the flux. Insoluble salts or insoluble oxides, which are substantially water impermeable materials, also can be used for this purpose. E.g.: poly ethylene glycol, polyhydric alcohols. A Wicking agent is defined as a material with the ability to draw water into the porous network of a delivery device. A wicking agent is of either swellable or non-swellable in nature. The function of wicking agent is to carry water to surfaces inside the core of the tablet, thereby creating channels or a network of increased surface area. E.g.: Colloidal silicon dioxide, SLS, PVP. An important part of the osmotic drug delivery system is the semipermeable membrane housing. Therefore, the polymeric membrane selection is important to the osmotic delivery formulation. Any polymer that is permeable to water but impermeable to solute can be used as coating material in osmotic devices. E.g.: Cellulose acetate, ethyl cellulose, Eudragits. Coating solvents suitable for making polymeric solution that is used for manufacturing the wall of the osmotic device include inert inorganic and organic solvents that do not adversely harm the core, wall and other materials. Plasticizers lower the temperature of the second order phase transition of the wall or the elastic modules of the wall and also increase the workability, flexibility and permeability of the fluids. Suitable polymers should have a high degree of solvent power for the materials, compatible with the materials over both the processing and the temperature range, exhibit permanence as seen by their strong tendency to remain in the plasticized wall, impart flexibility to the materials and should be non-toxic. E.g.: Dialkyl phthalates, triethyl citrate, propionates, glycolates.

 

Pore-forming agents are particularly used in the pumps developed for poorly water-soluble drug and in the development of controlled porosity or multiparticulate osmotic pumps. These pore forming agents cause the formation of microporous membrane. The microporous may be formed in situ by a pore former by its leaching during the operation of the system. Pores may also be formed in the wall by the volatilization of components in a polymer solution or by chemical reactions in the polymer solution. E.g.: Sodium chloride, potassium chloride, sodium bromide. Etoricoxib (5-chloro-2-[6-methylpyridin-3-yl]-3-[4- ethylsulfonylphenyl] pyridine) is a non-steroidal anti-inflammatory drug (NSAID)28. It is having the highest COX-2 selectivity and is used in the treatment of osteoarthritis and rheumatoid arthritis, acute gouty arthritis, acute dental surgery pain and similar conditions without affecting platelet function or damaging gastric mucosa. The major drawback of Etoricoxib is dry mouth and taste disturbances^{29, 30}. Etoricoxib belongs to the class of organic compounds known as bipyridines and oligopyridines. These are organic compounds which contain two pyridine rings linked to each other. Bioavailability of the drug is 100% following oral administration³¹. Based on the above observations, it was aimed to formulate and evaluate osmotic drug delivery systems for better release pattern and patient compliance.

 

MATERIALS AND METHODS:

Chemicals used:

Etoricoxib (Microlabs, Chennai), Lactose, Starch, Ethyl Cellulose (S D fine- chem Ltd, Mumbai), Hydroxy Propyl Methyl Cellulose (Lobachemie Pvt Ltd, Mumbai), Magnesium stearate (Otto kemi, Mumbai), Talc (S D fine- chem Ltd, Mumbai), Gelatin, Microcrystalline Cellulose, Cellulose Acetate, Propylene Glycol (Lobachemie Pvt Ltd, Mumbai), Polyvinyl Pyrrolidine (Sisco research laboratories Pvt Ltd, Mumbai), Sodium Chloride (S D fine- chem Ltd, Mumbai), Potassium Chloride (S D fine- chem Ltd, Mumbai), Sodium Lauryl Sulphate(S D fine- chem Ltd, Mumbai), Mannitol (Caplin point Laborotories Ltd), Methanol (Karnataka fine chem., Bangalore), Ethanol (Changshu Yangyuan Chemical, China) Acetone (Thermofisher Scientific India Pvt Ltd, Mumbai).

 

Instruments used:

FT/IR Spectroscopy/4100 (Jasco, Johannesburg, South Africa), Hydraulic/pellet press (Kimaya engineer, Thane, India), UV- Visible double beam spectrophotometer (Shimadzu, Shimadzu corporation, Philippines), Bulk and tapped density apparatus (Thermonik, Campbell electronics, Mumbai, India), Weighing balance (Shimadzu, Shimadzu corporation, Philippines), Hot air oven (Technico Chennai, India), Disintegration apparatus (Tab machines, Mumbai, India), Dissolution apparatus (Tab machines, Mumbai, India), Scanning electron microscope (JEOL, Japan), Stability chamber (Technico, Chennai, India).

 

Preparation of standard stock solution¹⁵:

The standard stock solution was prepared by dissolving 10mg of drug in 5ml of methanol to get a concentration of 1000mcg/litre. It was appropriately diluted with methanol to get a concentration of 100mcg/litre and was kept as stock solution.

 

Determination of λ max¹⁵:

The standard solution of Etoricoxib was scanned in UV spectrophotometer to obtain the maximum wavelength of absorption against blank between wavelengths of 200-400nm. The standard solution was scanned for absorbance maxima against blank. The maximum absorbance was found to be 234nm.

 

Preparation of calibration curve of etoricoxib¹⁵:

The stock solution of Etoricoxib was accordingly diluted to obtain concentration range of 0-10μg/ml. The absorbance was observed against methanol as blank and the calibration curve was plotted between concentration (x-axis) and absorbance (y-axis).

 

Preparation of granules of etoricoxib by wet granulation method¹⁶:

The active ingredient, Etoricoxib, and the excipients lactose, mannitol, MCC, and HPMC, were accurately weighed as per the quantities defined and were thoroughly mixed. Then the binding solution, which contains PVP K 30 dispersed in alcohol, was added. The prepared damp mass was sieved through sieve no #60 and dried in hot air oven. The dried mass was passed through sieve no#40 and blended with magnesium stearate and talc. The obtained granules were used for Preformulation studies.

 

Preparation and coating of self-pore forming osmotic tablets of etoricoxib¹⁶:

The above prepared granules were compressed to obtain Etoricoxib tablets. The coating solution was prepared by dissolving cellulose acetate and potassium chloride in a solvent mixture of acetone and methanol, using propylene glycol as plasticizer. The prepared tablets were coated using the coating solution.

 

Table 1: Formulation table of self-pore forming osmotic tablets of Etoricoxib¹⁶

Ingredients	Tablet core (mg)		Coating Solution
	F1	F2
Etoricoxib	90	90	-
Mannitol	50	40	-
Lactose	30	40	-
MCC	36	36	-
HPMC	36	36	-
PVP K 30 IN ethanol	10%	10%	-
Magnesium stearate	4	4	-
Talc	4	4	-
Cellulose acetate	-	-	3g
Polypropylene glycol	-	-	10ml
Potassium chloride	-	-	0.6g
acetone	-	-	80ml
methanol	-	-	20ml

 

Coating and filling of osmotic capsules of etoricoxib¹⁷:

Hard gelatin capsules of size 0 and 2 were taken. To make it insoluble in water, the gelatin capsules were treated with 1% solution of ethyl cellulose in ethyl alcohol and dried. The body part of capsule (size 2) was filled with a mixture of NaCl and gelatin in ratio (1:5). Another capsule of size 0 is taken and filled with Etoricoxib, sodium lauryl sulphate and starch. Then capsule (size 2) is inserted into the body of first capsule (size 0) and the caps are replaced. A hole is created at the top of capsule and then the capsules are placed in a de‐humidifier.

 

Table 2: Formulation table of osmotic capsules of Etoricoxib¹⁷

Ingredients	Quantity (mg)
	F3	F4	F5	F6
Etoricoxib	90	90	90	90
Sodium chloride	2	2	2	4
Starch	40	40	40	40
SLS	1%w/v	1.5%w/v	1%w/v	1%w/v
Gelatin	10	10	10	10
Ethyl cellulose in ethanol	1%	2%	1%	1%

 

Preformulation studies:

The discovery and development of new chemical entities (NCEs) into stable, bioavailable, marketable drug products is a long, but rewarding process. Once an NCE is selected for development, choosing the molecular form that will be the active pharmaceutical ingredient (API) is a critical milestone because all subsequent development will be affected by this decision. A well- designed preformulation study is necessary to fully characterize molecules during the discovery and development process, so that NCEs have the appropriate properties, and there is an understanding of the deficiencies that must be overcome by the formulation process.^18,19. The procedure of each preformulation test suitable for tablets and capsules which includes Compatibility Studies IR spectra matching approach, angle of repose by fixed funnel method. The bulk density was determined by pouring pre-sieved, Tapped density, Compressibility Index/ Carr’s Index, Hausner’s Ratio.

 

Post preformulation studies:

I) Tablets^{10, 19}:

a) Weight variation test:

20 tablets were selected. They were individually weighed and average weight was determined. The individual weights of the tablets were compared to the average weight.

 

b) Coating uniformity:

The uniformity of coating among the tablets can be estimated by determining the weight of the tablets before and after the coating.

 

c) Coat thickness:

The coat thickness can be determined from depleted devices following careful washing and drying of the film, using digital Vernier calipers.

 

d) Hardness test:

It can be determined using a Pfizer type or Monsanto type hardness tester. The pressure required to break the tablet into fragments is determined. The minimum value required for a tablet is 4 Kg/cm².

 

e) Friability test:

Friability can be determined using a Roche friabilator. 10 tablets were weighed initially. It was then put into the drum of the friabilator. The drum rotates at a speed of 25 rpm. The drum is operated for 100 revolutions. The tablets were then removed, dusted and re-weighed.

 

II) Capsules^10,19:

a)    Weight variation test:

20 capsules were selected randomly. Weigh individual capsules intact. Opened the capsule without losing any of the contents and remove the contents as completely as possible. Weigh the shell. The weight of the contents is the difference between the weights. Repeat the procedure for the remaining 19 capsules. Determine the average weight.

 

 

b)    Orifice diameter:

The mean orifice diameter of osmotic pump capsule can be determined microscopically using pre-calibrated ocular micrometer. Random selection of capsules was done.

 

Common tests for osmotic tablets and capsules^10,19:

a) Disintegration test:

The disintegration test apparatus contains 6 glass tubes. One tablet is placed in each tube. The medium used is hydrochloric acid buffer of pH 1.2 initially (which resembles the stomach pH), followed by phosphate buffer of pH 6.8 (which resembles the intestinal pH). The medium is maintained at 37º±2ºC. A motor moves the basket assembly up and down through a distance of 5-6cm at a frequency of 28-32 cycles/min. The time when all the fragments of the tablet disintegrate and pass through the mesh screen is taken as the disintegration time.¹⁹

 

b) Dissolution studies:

This test was carried out by using USP XXIV dissolution test apparatus Type I basket type for capsules and Type II paddle type for tablets. The study is conducted for 12 hours using 900ml hydrochloric acid buffer of pH 1.2 initially for 2 hours, followed by phosphate buffer of pH 6.8 for the remaining 10 hours. The dissolution medium was kept at in a thermostatically controlled water bath at 37º±0.5ºC. The dosage forms were introduced into the dissolution medium. The medium was stirred at 50 rpm. At predetermined time intervals, 5ml of samples were withdrawn and analyzed spectrophotometrically at 234 nm. At each time of withdrawal 5mL of fresh corresponding medium was replaced into the dissolution bowl. The cumulative amount of drug release was calculated and plotted against time.¹⁵

 

Tests for optimized osmotic tablet:

a)    Effect of different ph phosphate buffers on drug release:

An osmotically controlled release system delivers its contents independently of external variables. To check this, dissolution media with different pH (1.2, 5, 6.8 and 8) was used.

 

b)    Effect of agitation intensity:

In order to study the effect of agitation intensity of the release media, release studies is carried out in dissolution apparatus at various rotational speeds (25,50,75 and 100 rpm).

 

Scanning electron microscopy²⁰:

The morphology of the coating membrane of optimized formulation F1obtained before and after complete dissolution of core contents were examined for their porous morphology by scanning electron microscope (JEOL JSM‐6300, Japan) at Karunya university, Coimbatore. Membranes were dried at 45°C for 12 h and stored in a dessicator until examination. A scanning electron microscope with a secondary electron detector was used to obtain digital images of the coating.

 

Release kinetic analysis:

To study the release kinetics, data obtained from in vitro drug release studies were plotted in various kinetic models.

 

Mechanism of drug release:

To evaluate the mechanism of drug release for Etoricoxib osmotic dosage forms, data of drug release were plotted in Korsmeyer et al’s equation as log cumulative percentage of drug released vs. log time, and the exponent n and was calculated through the slope of the straight line.

 

Stability studies:

Stability studies were conducted by storing the tablets and capsules at 40oC±20C, 70% RH ±5% for 45 days. The samples were withdrawn at initial, 30th & 45th day and analyzed suitably for the physical characteristics, weight variation, friability, disintegration time and % cumulative drug release.

 

RESULTS AND DISCUSSIONS:

Calibration curve of etoricoxib¹⁵:

A calibration curve for Etoricoxib was constructed by dissolving the drug in methanol. λ max was determined by scanning between wavelengths of 200-400 nm. The linearity of the curve was found in the range of 0- 10µg/ml. The wavelength was determined to be 234 nm. A regression coefficient value of 0.998 was obtained.

 

Figure 1: Calibration curve data of Etoricoxib

 

Compatibility studies:

The IR spectra of pure drug, Etoricoxib and polymers was analyzed and compared with IR spectra obtained for mixtures. The results showed that the drug and excipients in the formulation were not having any interaction.

 

Table 3: Characteristic peaks of Etoricoxib and excipients

 

Preformulation studies^20,21:

The preformulation study of the prepared Etoricoxib granules showed the followings:

Angle of repose at a range between = 24 0 13’ to 260 21’

Bulk density at a range between = 0.284gm/cm3 to 0.292gm/cm3

Tapped density at a range between = 0.335gm/cm3 to 0.346gm/cm3

Hausner’s ratio at a range between = 1.17 to 1.18

Carr’s index at a range between = 15.22% to 15.60%

 

From above values it was observed that the all formulations showed the good to fair flow properties. F1 formulation showed good flow property.

 

Post formulation studies:

Table 4: Results of post formulation studies of osmotic tablets²²

Form code		F1	F2
Weight variation	Before coating	250 ± 0.66	249 ± 1.22
	After coating	255 ± 0.24	256 ± 0.76
	1	40	45
	2	40	50
	3	30	40
Hardness (kg/cm3)		6.5	6
Friability (%)		0.01	0.02
Disintegration time (mins)		326	294

 

From the values obtained for all the formulations, weight variation was in the range of 249-250 mg (for uncoated tablets), 255-256 mg (for coated tablets), coat thickness was in the range of 30-50 µm, hardness was in the range of 6 - 6.5 Kg/cm3 , friability was in the range of 0.01- 0.02 % and disintegration time was in the range of 294-326 mins.

 

Table 5: results of post formulation studies of osmotic capsules¹⁷

Form code	Weight variation (mg)	Disintegration time (mins)	Orifice diameter (mm)
			1	2	3
F3	152 ± 0.82	28	0.46	0.44	0.45
F4	157 ± 0.67	32	0.44	0.46	0.44
F5	152 ± 0.33	29	0.48	0.42	0.42
F6	154 ± 0.56	28	0.44	0.42	0.42

 

Figure 2: Determination of orifice diameter by micrometry

 

From the values obtained for all the formulations, weight variation was in the range of 152-157 mg, disintegration time was in the range of 28– 32mins and orifice diameter was in the range of 0.42–0.48 mm.

 

In vitro dissolution studies:

 

Figure 3: In vitro drug release of different prepared osmotic formulations In vitro release study was performed for all the prepared formulations.

 

In vitro release was performed for all the prepared formulations. The plots were drawn by taking time vs percentage cumulative release. It was observed that all the formulations showed the % cumulative release in the range of 68.56 – 90.78%. The formulation F1 showed a slower release pattern which was desired for sustained release. The formulation F1 showed a maximum release of 68.56% at 12^th hour.

 

Tests for optimized osmotic tablets:

 

Figure 4: Effect of different pH phosphate buffers on drug release

 

 

Figure 5: Effect of agitation intensity on drug release

 

Different pH phosphate buffers were prepared and the effect of pH on drug release from the F1 formulation was studied. It was found that different pH doesn’t have significant effects on drug release. At 6th hour, the maximum release was 32.78% at pH 2, 32.33% at pH 5, 32.43% at pH 6.8 and 33.09% at pH 8.

 

Different agitation intensities were used and the effect on drug release from the F1 formulation was studied. It was found that different agitation intensity doesn’t have significant effects on drug release. At 6th hour, the maximum release was 32.80% at 25 rpm, 32.38% at 50 rpm, 32.43% at 75 rpm and 32.29% at 100 rpm.

 

Scanning electron microscopy²⁰:

 

Figure 6: Scanning Electron Microscopy of F1 osmotic tab

(a) Before dissolution b) after dissolution

 

The morphology of the coating membrane of optimized formulation F1 before and after complete dissolution of core contents were examined. After dissolution, it showed numerous pores, through which the drug release occurs.

 

Release kinetic analysis:

Table 6: Results of kinetic analysis

Formulation	Zero order	First order	Higuchi model	Korsmeyer-peppas model
	R2	R2	R2	n	R2
F1	0.994	0.781	0.818	0.935	0.980

 

Stability studies:

Table7: Stability studies of F1 formulation

Si No	Parameters	Initial	30th day	45th day
1	Physical appearance	white	white	White
2	Weight of coated tablets(mg)	255± 0.66	255 ± 0.68	255 ± 0.68
3	Friability (%)	0.01	0.01	0.01
4	Disintegration time (mins)	326	321	321
5	% cumulative release at 12thhr	68.56	65.45	64.09

 

Stability studies of best formulation (F1) was carried out at Accelerated temperature at 40° ± 2°C, and RH 70 % ± 5 % in humidity control oven for 45 days. After 45 days the sample was evaluated for the physical appearance, weight variation, friability, disintegration time and in vitro drug release studies. After the study for 45 days, it was concluded that there was no major changes in the various parameters evaluated like physical appearance, weight, friability, disintegration time and in vitro dissolution profile of F1 at 40° ± 2°C, and RH 70 % ± 5 %. Thus, it can be concluded that F1 is stable at a temperature of 40° ± 2°C and relative humidity of 70 % ± 5 % for a period of 45 days.

 

 

CONCLUSION:

Osmotic drug delivery systems deliver the drugs based on the phenomenon of osmosis. Osmosis is defined as the spontaneous movement of solvent from a solution of lower solute concentration to a solution of higher solute concentration through a semi-permeable membrane. These osmotic systems can overcome the drawbacks of many conventional dosage forms as their absorption from the GIT is independent of the gastric pH, peristaltic movements and presence of food. In this work, a successful attempt was made for formulating osmotic drug delivery systems of Etoricoxib in the treatment of inflammation and arthritis. Wet granulation technique is used in the preparation of Etoricoxib granules by using PVP K 30 in ethanol as binder. Various osmogens were employed, which controlled the release of the drug from the systems. Out of the 6 formulations, F1 (osmotic tablet) which contained equal proportion of mannitol and lactose as osmogens, was selected as the best formulation based on the preformulation parameters, and the release pattern (68.56%).

 

ACKNOWLEDGEMENT:

The authors are grateful to the authorities of KMCH College of Pharmacy, Coimbatore for the facilities.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

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Received on 05.05.2019           Modified on 18.07.2019

Accepted on 11.09.2019         © RJPT All right reserved