Development and Evaluation of Controlled Porosity Osmotic Pump Tablets for Zidovudine and Lamivudine Combination

Chinmaya Keshari Sahoo¹*, Surepalli Ram Mohan Rao², Muvvala Sudhakar³

¹Ph.D Scholar, Department of Pharmaceutics, Faculty of Pharmacy, University College of Technology,

Osmania University, Hyderabad, Telangana-500007.

²Professor, Mekelle Institute of Technology, Mekelle University, Mekelle, Ethiopia.

³Professor and Principal, Department of Pharmaceutics, Malla Reddy College of Pharmacy, Maisammaguda, Secunderabad, Telangana-500014.

*Corresponding Author E-mail: sahoo.chinmaya83@gmail.com

ABSTRACT:

The present work was aimed to develop and evaluate controlled porosity osmotic pump (CPOP) tablets of zidovudine-lamivudine combination for the treatment of AIDS. The tablets were prepared by wet granulation method incorporating drug, various excipients, controlled release polymer hydroxyl propyl methyl cellulose (HPMCE5M LV) and osmogen (Mannitol) in the core. The CPOP tablets consist of an osmotic core coated with a micro porous membrane made up of cellulose acetate (CA) which is incorporated with sorbitol as porogen. Prior to compression the prepared granules were evaluated for pre compression parameters such as angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. After compression the prepared granules were evaluated for thickness, coat thickness, hardness, weight variation, friability, drug content, diameter, in vitro drug release study and scanning electron microscopy (SEM) study. The release kinetics for different formulations were analyzed using zero order model equation, first order model equation, Higuchi model equation, Korsmeyer Peppas model equation and Hixson-Crowell equation. The optimized formulation of drug release was independent of pH, agitation intensity, but dependent on the osmotic pressure of the release media. FTIR and DSC study revealed that there was no interaction between drug and excipients. Formulations subjected to stability testing (at 40±2ºC/75±5% RH) as per ICH guidelines for three months indicated stability with no significant changes in thickness, hardness, weight variation, friability, drug content and dissolution profiles.

KEYWORDS: CPOP, Zero order, Cellulose acetate, SEM, DSC.

INTRODUCTION:

AIDS is the final stage [1] of infection where HIV damages the immune system, the body lacks fighting against opportunistic infections. AIDS is spread by unprotected sexual intercourse, contaminated blood transfusions, hypodermic needles and from mother to child during pregnancy, delivery or breastfeeding and certain body fluids from a person infected with HIV such as semen, pre seminal fluid, vaginal fluid and breast milk. People living with AIDS experiences CD4+ count of less than 200cells/µL in blood. There is no cure for HIV infection, but medicines can prevent advancing of disease by inhibiting growth of HIV in body and helps people with HIV live longer.

The therapy for the treatment of HIV infection comprises different classes [2] such as nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and fusion inhibitors. The monotherapy acts an early stage in the HIV life cycle by blocking the activity reverse transcriptase. This enzyme is utilized for the conversion of viral RNA to proviral DNA, thus allowing integration into host cell DNA and subsequent viral replication. Hence combination therapy [3] is considered to be the standard of care of HIV infected patients. These therapeutic regimens result however in a great number of daily doses of tablets/capsules. The current formulation containing 150 mg of lamivudine and 300 mg zidovudine has been developed as an oral therapy (tablet) for the treatment of HIV-1 infection in adults. The development of this fixed dose combination aims to reduce the number of daily tablets, and therefore enhance the compliance therapy and thereby minimizing the risk of emergence of resistance

Oral conventional drug delivery system lacks control drug release and effective concentration of drug at the target site and mostly affected by physiological conditions of body. To avoid these limitations of conventional drug delivery [4] system modified release drug products can be designed to control release rate of drug and time of drug release. Out of various modified drug release product extended release dosage forms allow at least a twofold reduction in frequency in dosage frequency as compared to conventional dosage form. Controlled release dosage forms is a part of extended release dosage form cover a wide range of prolonged action which provide continuous release of their active ingredients at predetermined rate [5] and predetermined time. Out of various controlled drug delivery systems osmotic controlled drug delivery system (OCDDS) is one of the most promising drug delivery technologies that use osmotic pressure for controlled delivery of drugs [5]. OCDDS deliver the drug in a large extent and the delivery nature is independent of physiological factors of gastrointestinal tract, independent of pH, hydrodynamic condition of the body and agitation intensity [7]. The current work is to design controlled porosity osmotic pump tablets of zidovudine-lamivudine combination. In CPOP delivery orifice is formed by the incorporation of water leachable component in the coating. Once the tablet comes in contact with aqueous environment, the water soluble additives dissolves and osmotic pumping results. Hence water diffuses into the core through the micro porous membrane [6] setting up an osmotic gradient and followed by controlling the release of drug. The present study is to develop controlled porosity osmotic pump tablets. The rate of drug delivery depends upon the factors such as water permeability of the semi permeable membrane, osmotic pressure of core formulation, thickness and total area of coating.

MATERIALS AND METHODS:

Materials:

Zidovudine and lamivudine were obtained from Hetero Drugs Pvt. Ltd. India. Mannitol was purchased from Qualigens Fine Chemicals, India. Cellulose acetate (CA) was obtained from Eastman Chemical Inc, Kingsport, TN. Sorbitol, HPMC E5M LV, magnesium stearate, talc and polyethylene glycol (PEG) 400,600,4000,6000 were purchased from S.D. Fine Chemicals Ltd, Mumbai, India. Microcrystaline cellulose (MCC), starch all is purchased from Signet Pharma, Mumbai, and India. All other solvents and reagents used were of analytical grade.

Compatibility studies:

Fourier Transform Infrared Spectroscopy (FTIR):

In this method individual samples as well as the mixture of drug and excipients were ground mixed thoroughly with potassium bromide (1:100) for 3-5 minutes in a mortar and compressed into disc by applying pressure of 10kg/cm to form a transparent pellet in hydraulic press. The pellet was kept in the sample holder and scanned from 4000 to 400 cm^-1in FTIR spectrophotometer (Bruker, Germany).

Differential Scanning Calorimetry (DSC):

Physical mixtures of drug and individual excipients in the ratio of 1:1 were taken and examined in DSC (Shimadzu DSC-50, Japan).Individual samples as well as physical mixture of drug and excipients were weighed to about 5mg in DSC pan. The sample pan was crimped for effective heat conduction and scanned [8] in the temperature range of 50-300⁰C.Heating rate of 20⁰C min^-1was used and the thermogram obtained was reviewed for evidence of any interactions.

Methods:

Preparation of osmotic pump tablets:

Wet granulation technique [9] was used to develop CPOP core tablets. Accurately weighed quantities of ingredients mentioned in Table 1 were sifted through sieve No. 30. Lubricant (magnesium stearate) and glidant (talc) were sifted through sieve No. 80.The ingredients were manually blended homogenously in a mortar by way of geometric dilution except lubricant and glidant. The mixture was moistened with aqueous solution and granulated through sieve No.30 and dried in a hot air oven at 60ºC for sufficient time (3-4 hrs). The dried granules were passed through sieve No.30 and blended with talc and magnesium stearate. The homogenous blend was then compressed into round tablets with standard concave punches using 10 station rotary compression machine (Mini press, Karnavati, India).

Table 1: Composition of CPOP tablets of zidovudine-lamivudine combination

Ingredients (mg)	CM1	CM2	CM3	CM4
ZD	300	300	300	300
LD	150	150	150	150
MCC	150	120	90	60
Starch	50	50	50	50
HPMC E5LV	60	60	60	60
Mannitol	30	60	90	120
Magnesium stearate	5	5	5	5
Talc	5	5	5	5
Total weight(mg)	750	750	750	750

Coating of core tablets:

The coating [10] solution was prepared taking required ingredients from table 2 and acetone was added quantity sufficient maintaining proper viscosity of solution. The coatings of tablets were performed by spray pan coating in a perforated pan (GAC-205, Gansons Ltd, Mumbai, India). Hot air is supplied to tablet bed by rotating lower speed 5-8 rpm initially. The coating of tablets was carried out with the rotation speed of 10-12 rpm.The spray rate and atomizing air pressure were 4-6 ml/min and 1.75 kg/cm²respectively. Inlet and outlet air temperature were 50ºC and 40ºC respectively. Coated tablets were dried at 50ºC for 12 hrs.

Evaluation of granules:

The prepared granules [11] were evaluated for pre compression parameters such as angle of repose, bulk density, tapped density and compressibility index (Carr’s index).Fixed funnel method was used to estimate angle of repose. The bulk density and tapped density were evaluated by bulk density apparatus (Sisco, India).

The Carr’s index [12] is calculated by the following formula.

%Carr’ sindex100 (1)

Where e_t is the tapped density of granules and e_b is bulk density of granules.

Hausner’s ratio was calculated by the taking the ratio of tapped density to the ratio of bulk density.

Evaluation of tablets [13]:

Thickness:

The thickness of individual tablets is calculated by using vernier caliper (Absolute digimatic, Mitutoyo Corp. Japan).The limit of the thickness deviation of each tablet is 5%.

Measurement of coat thickness:

Film was isolated from the tablets after dissolution and dried at 40⁰C for 1hr.Thickness was measured by using electronic digital calipers (Absolute digimatic, Mitutoyo Corp. Japan)

Hardness:

The hardness of tablets can be determined by using Monsanto hardness tester (Sisco, India).

Friability test:

Friability test of tablets was performed in a Roche friabilator (Sisco, India).Twenty tablets of known weight (W₁) were de-dusted in plastic chamber of friabilator for a fixed time of 25 rpm for 4 minutes and weighed again of weight (W₂).The percentage of friability was calculated using the following equation.

%Friability (2)

Where, W₁ and W₂ are the weight of the tablets before and after the test respectively.

Weight variation test:

The weight variation test is conducted by weighing 20 tablets individually calculating the average weight and comparing the individual tablet weights to the average. The percentage weight deviation was calculated and then compared with USP specifications.

Uniformity of drug content test:

Powder is made after triturating 10 CPOP tablets from each batch with mortar and pestle. The powder weight equivalent to one tablet was dissolved in a 100ml volumetric flask filled with 0.1N HCl using magnetic stirrer for 24hr.Solution was filtered through Whatman filter paper No.1 diluted suitably and analyzed spectro photometrically

Diameter of tablet:

The diameter of individual tablets is measured by using vernier caliper (Absolute digimatic, Mitutoyo Corp. Japan).

In vitro dissolution studies:

The in vitro dissolution studies [14] were carried out using USP apparatus type II (Lab India 8000) at 75 rpm. For the first 2 hr the dissolution medium was 0.1N HCl (pH1.2) and phosphate buffer pH 6.8 from 3-8 hr (900 ml), maintained at 37±0.5⁰C. At each time point 5 ml of sample was withdrawn and it was replaced with 5 ml of fresh medium. The drug release at different time interval was measured by UV-visible spectrophotometer (UV-1800, Shimadzu, Japan).It was evaluated for both the drugs in different wavelengths.

In vitro drug release kinetic studies:

In order to observe [15] the mode of release from tablets, the release data of formulation was analyzed zero order kinetics, first order kinetics, Higuchi model, Korsmeyer and Peppas and Hixson-Crowell equations.

Zero order kinetics for drug release can be expressed by the equation

Q_t = Q₀K₀t (3)

Where

Q_t is the amount of drug dissolved in time t, Q₀ is the initial amount of drug in the solution and K₀ is the zero order release constant. The release kinetics can be studied by plotting cumulative amount of drug release versus time.

First order kinetics for drug release can be expressed by the equation:

Log C = log C₀K₁t/2.303 (4)

Where C₀ is the initial concentration of drug, C is the amount of drug remaining to be released in time t, K₁ is the first order release constant. The release kinetics can be studied by plotting log cumulative percentage of drug remaining versus time. The first order release constant K₁ can be obtained by multiplying 2.303 with slope.

Higuchi model [16] for drug release from matrix devices can be expressed by the equation.

Q = K_H √ t (5)

Where Q is the amount of drug release in time t, K_H is the Higuchi dissolution constant. The release kinetics can be studied by plotting cumulative percentage of drug release versus square root of time. The slope is equivalent to K_H.

Korsmeyer-Peppas model (KP Model) [17] for mechanism of drug release can be expressed as

Log (M_t/M_∞) Log K n Log t (6)

Where M_t is the amount of drug release at time t, M_∞ is the amount of drug release after infinite time, K is the release rate constant incorporating structural and geometric characteristics of the tablet and n is the release exponent indicative of mechanism of drug release. The release kinetics can be studied by plotting log cumulative percentage drug release versus log time. In case of tablets (which are of cylindrical shape) a value of n 0.45 indicates Fickian or Case I release;a value between 0.45n0.89 shows non-Fickian or anomalous release;n0.89 for case II release and n0.89 indicates super case II release.

Hixson and Crowell model [18] for mechanism of drug release can be expressed by the equation

W₀^1/3 W_t^1/3 κ t (7)

Where W₀ is the initial amount of drug in the pharmaceutical dosage form, W_t is remaining amount of drug in the pharmaceutical dosage form at time t and κ is proportionality constant incorporating the surface volume relation. The release kinetics can be studied by plotting cube root of drug percentage remaining in matrix versus time.

Effect of osmogen concentration [19]:

Keeping all the parameters for a tablet constant different osmogen concentrations were used to prepare tablets. The drug release was compared with the different osmogen concentration of formulated batches by using USP-II dissolution apparatus.

Effect of pore former concentration [20]:

SPM for various batches were prepared by taking different concentrations of pore former. The effect of pore former on in vitro release profile is compared as well as number of formation of micropores were observed.

Effect of membrane thickness [21]:

Tablets with varying coating thicknesses were developed to demonstrate the effect of coating thickness on drug release. The drug release rate was measured using 0.1N HCl and phosphate buffer pH6.8 as a dissolution medium.

Effect of osmotic pressure [22]:

The effect of osmotic pressure was analyzed by adding different amount of mannitol of an osmotic agent to produce 30 atm, 60 atm and 90 atm respectively in dissolution media 0.1N HCl for 2hrs and phosphate buffer pH 6.8 for remaining hours. The drug release rate was carried out in USP type II (Paddle) apparatus at 75 rpm maintained at 37±0.5⁰C and compared for various dosage forms.

Effect of pH [23]:

The effect of pH for developed formulations were observed by performing the release studies of optimized formulation in different media 0.1 N HCl(pH 1.2), pH 6.8 phosphate buffer and pH 7.4 phosphate buffer in USP type II dissolution apparatus at 75rpm. The temperature was maintained at 37±0.5°C. The release was studied at predetermined time intervals.

Effect of agitation intensity [24]:

The effect of agitation intensity were observed by performing the release studies of optimized formulation in USP Type II(Paddle) dissolution apparatus containing 0.1NHCl for first 2hrs and phosphate buffer pH 6.8 for remaining hours at different rotational speeds of 50,100 and 150rpm with maintaining temperature at 37±0.5°C.The samples were withdrawn at predetermined intervals and analyzed by UV spectrophotometer.

Scanning Electron Microscopy (SEM) [25]:

Coating membranes of formulation were collected before and after complete dissolution of core contents and examined for their porous morphology as well as mechanism of drug release by scanning electron microscope (Leica, Bensheim, Switzerland). Scans were taken at an excitation voltage in SEM fitted with ion sputtering device.

Accelerated stability studies [26]:

The packed tablets in air tight container were placed in stability chambers(Thermo lab Scientific equipment Pvt. Ltd., Mumbai, India) maintained at 40±2⁰C/75±5% RH conditions for accelerated testing) for 3 months. Tablets were periodically removed and evaluated for physical characteristics, drug content, in‐vitro drug release etc.

RESULTS ANS DISCUSSION:

FTIR studies:

Figure 1 shows the characteristic absorption peaks of zidovudine for the carbonyl group at 1638.76 cm^-1, N=N⁺=N stretching (azido group) at 2114.50 cm^-1,C-O stretching at 1063.08 cm^-1 and amine group stretching at 3317.86 cm^-1. Figure 2 shows the characteristic absorption peaks of lamivudine for the C-H stretching at 2843.83 cm^-1, N-H bending at 1640.32 cm^-1,C-N stretching at 1010.71 cm^-1,O-H in plane bending at 1054.55 cm^-1 and amine group stretching at 3326.6 cm^-1.The major peaks of HPMCE5LV were found at 3880.71, 3810.87, 3713.83, 3669.20, 3601.84, 3566.74, 3557.95, 3473.68, 3222.79, 3117.03, 3066.96, 2982.59, 2887.86, 2847.2, 2803.12, 2710.75, 2618.99, 2444.13, 2335.14, 2068.70, 1661.47, 1536.52, 1500.67, 1424.62, 1071.87, 781.05 and 584.97 cm^-1. The major peaks of mannitol were found at 2986.88, 2900.97, 1646.58, 1394.32, 1251.01, 1230.06, 1050.08, 1015.87 and 669.43 cm^-1.In the optimized (Figure 3) formulation CM4 peak at 3675.48,1448.33, 1251.22 and782.59 cm^-1were due to presence of the polymer HPMCE5LV.In the formulation the peaks present due to mannitol were 2986.96,1229.74 and 687.37 cm^-1.Peaks at 3299.24 and 1065.88cm^-1 were due to presence of the drug zidovudine in the optimized formulation and peaks at 1005 and 1616.34 cm^-1 were due to presence of the drug lamivudine. Hence it is observed that the major peaks of drug 3299.24, 1616.34, 1065.88 and1005cm^-1 remain unchange and no interaction was found between the drug, polymer and osmogen.

Figure 4:DSC study of zidovudine

Figure 5: DSC study of lamivudine

Figure 6: DSC study of CM4

Table 3: Pre compression parameters of powder blend

Formulation code	Angle of repose (degree)^a± S.D	Bulk density (gm/ml)^a± S.D	Tapped density (gm/ml)^a± S.D	Carr’s Index (%)^a± S.D	Hausner’s Ratio^a± S.D
CM1	28.76±0.08	0.499±0.08	0.544±0.06	8.27±0.04	1.09±0.12
CM2	27.34±0.06	0.509±0.11	0.545±0.13	6.60±0.08	1.07±0.16
CM3	26.10±0.02	0.502±0.08	0.544±0.14	7.72±0.08	1.08±0.11
CM4	25.12±0.03	0.496±0.06	0.529±0.12	6.23±0.09	1.06±0.12

All values are expressed as mean ±S.D, a n = 3

Table 4: Post compression parameters of CPOP tablets

Formulation code	Thickness (mm)^a± S.D	Coat thickness (µm)^a± S.D	Hardness (kg/cm²)^a ±S.D	%Friability (%)^b± S.D	%Weight variation (%)^b	%Drug content (%)^a ± S.D(ZD)	%Drug content (%)^a ± S.D (LM)	Diameter (mm)^a± S.D
CM1	4.02±0.02	250.1±3.2	6.8±0.13	0.23±0.08	1.54±0.24	98.61±0.85	98.51±0.85	10.19±0.06
CM2	4.01±0.12	200.8±2.9	6.9±0.12	0.18±0.07	1.42±0.16	99.72± 0.77	99.68± 0.77	10.96±0.03
CM3	4.03±0.13	150.7±2.8	7.1±0.13	0.14±0.06	1.08±0.11	98.88±0.67	98.46±0.67	10.13±0.04
CM4	4.00±0.09	100.8±3.2	7.2±0.12	0.11±0.03	1.17±0.31	100.27±0.56	100±0.56	10.06±0.05

N.B.-All values are expressed as mean± S.D, ^an = 10,^bn = 20

Table 5: Fitting of IVDR data for zidovudine from combination in various mathematical models

Models(Z)	Zero order		First order		Higuchi		Korsmeyer-Peppas			Hixson-Crowell
Batches	R²	K₀	R₁²	K₁	R_H²	K_H	R_K²	Kkp	n	R²	Ks
CM1	0.968	9.699	0.990	0.202	0.976	29.69	0.984	21.13	0.644	0.994	0.240
CM2	0.956	9.979	0.991	0.223	0.983	30.84	0.981	23.87	0.608	0.993	0.259
CM3	0.951	10.42	0.980	0.260	0.981	32.27	0.970	26.60	0.575	0.987	0.289
CM4	0.918	10.64	0.970	0.333	0.992	33.72	0.979	34.27	0.485	0.984	0.336

Table 6: Fitting of IVDR data for lamivudine from combination in various mathematical models

Models (L)	Zero order		First order		Higuchi		Korsmeyer-Peppas			Hixson-Crowell
Batches	R²	K₀	R₁²	K₁	R_H²	K_H	R_K²	Kkp	n	R²	Ks
CM1	0.909	9.460	0.992	0.216	0.996	30.19	0.994	29.92	0.504	0.978	0.249
CM2	0.878	9.491	0.991	0.234	0.994	30.79	0.996	34.27	0.454	0.97	0.262
CM3	0.876	10.02	0.991	0.276	0.991	32.49	0.988	36.05	0.455	0.972	0.296
CM4	0.824	10.05	0.992	0.347	0.979	33.4	0.991	44.46	0.377	0.969	0.338

Effect of osmogen concentration:

The various batches of CPOP tablets were developed with various concentration of osmogens. It was observed that osmogent enhances the drug release of drug and thus had a direct effect on drug release. The drug release profile was shown in figure 7 for zidovudine and figure 8 for lamivudine.

Effect of pore former concentration:

The core formulations were coated with various concentration of sorbitol with compared to CA. It confirms that as the level of pore former increases the membrane becomes more porous after coming contact with aqueous environment resulting in faster drug release. The drug release profile was shown in figure 7 for zidovudine and figure 8 for lamivudine.

Effect of membrane thickness:

Release profiles of CPOP tablets from various batches varying the coating thickness were evaluated. It was clearly evident that drug release was inversely proportional to coating thickness of the semi permeable membrane. The drug release profile was shown in figure 7 for zidovudine and figure 8 for lamivudine.

Effect of osmotic pressure on optimized formulation:

The results of release studies of optimized formulation in media of different osmotic pressure indicated that the drug release is highly dependent on the osmotic pressure of the release media. The release was inversely related to the osmotic pressure of release media. This finding confirms that the mechanism of drug release is by osmotic pressure. The drug release of zidovudine for CM4 was found to be 89.11% for 30 atm, 85.46% for 60 atm and 81.09% for 90 atm respectively. It is shown in figure 9.Similarly the drug release of lamivudine for CM4 was found to be 91.24% for 30 atm, 87.12% for 60 atm and 83.11% for 90 atm respectively. It is shown in figure 10.

Figure 9: In vitro release profiles showing Zidovudine release from best CM4 in different osmotic pressures

Figure 10: In vitro release profiles showing Lamivudine release from best CM4 in different osmotic pressures

Effect of pH:

The optimized formulation CM4 was subjected to in vitro drug release studies of zidovudine(Figure 11) and lamivudine (Figure 12) differently in buffers with different pH like pH 1.2, pH 6.8 and pH7.4. It is observed that there is no significant difference in the release profile for lamivudine and zidovudine from combination, demonstrating that the developed formulation shows pH independent release.

Figure 11: In vitro dissolution study of zidovudine from best formulation CM4 in various pH media

Figure 12: In vitro dissolution study of Lamivudine from best formulation CM4 in various pH media

Effect of agitation intensity:

The optimized formulation of CM4 batch was carried out in USP dissolution apparatus type-II at varying rotational speed(50,100 and 150rpm) for zidovudine and lamivudine from combination(Figure 13,14).It shows that the release of both the drugs from CPOP is independent of agitation intensity. Hence it can be expected that the release from the developed formulation will be independent of the hydrodynamic conditions of the absorption site.

a) SEM before dissolution b) SEM after dissolution

Figure 15: a) SEM of membrane structure of optimized formulation before dissolution, b) SEM of membrane structure of optimized formulation after dissolution

Table 7: Comparative physicochemical characterization of CM4 at accelerated conditions

Sl. no.	Parameters	Initial	After 30 days	After 60 days	After 90 days
1.	Physical appearance	Pale white,circular,concave smooth surface without any cracks	No change	No change	No change
2.	Thickness(mm)^a ± S.D	4.00±0.09	4.00±0.09	4.00±0.09	4.01±0.08
3	Hardness(kg/cm²)^a ± S.D	7.2±0.12	7.2±0.13	7.1±0.11	7.1±0.12
4.	Friability(%)^a ± S.D	0.11±0.03	0.11±0.03	0.12±0.06	0.13±0.08
5	Weight variation(mg)^b ± S.D	1.17±0.31	1.17±0.31	1.18±0.31	1.19±0.31
6.	Drug content(%)^a ± S.D(ZD)	100.27±0.56	100.27±0.56	100.18±0.41	100.07±0.22
7.	Drug content(%)^a ± S.D(LM)	100±0.56	100±0.56	100±0.25	99.8±0.52

N.B.-All values are expressed as mean± S.D, ^an = 10,^bn = 20

CONCLUSION:

From the developed CPOP formulations it was evident that increase in concentration of osmogen the drug release from the system was found to be increased. The optimized formulation was independent of pH and agitation intensity. Finally it was concluded that the release of optimized formulation is significantly controlled from the controlled porosity osmotic delivery system and thus it is a promising approach for the treatment of AIDS.

ACKNOWLEDGEMENTS:

The authors would like to acknowledge the contributions of Pharmaceutics Department, Faculty of Pharmacy, University College of Technology Osmania University, Hyderabad, Telangana, India for providing necessary facilities to carry out the research work. This study was part of a Ph.D thesis under Osmania University, Hyderabad.

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Received on 10.05.2017 Modified on 19.06.2017

Research J. Pharm. and Tech. 2017; 10(8): 2591-2601.

DOI: 10.5958/0974-360X.2017.00460.7

Formulation code	CA (g)	PEG 400 (g)	PEG 600 (g)	PEG 4000(g)	PEG 6000 (g)	Sorbitol (g)	Acetone (mL)
CM1	6	2	0	0	0	0	300
CM2	6	0	2	0	0	0.6	300
CM3	6	0	0	2	0	1.2	300
CM4	6	0	0	0	2	1.8	300