INTRODUCTION:

Nanosponges are a novel class of nanoparticles with nanostructured hyper branched polymers and few nanometres wide cavities. Nanosponges are porous polymeric delivery systems that are small spherical particles with large porous surface. These are tiny sponges with a size of about a virus with an average diameter below 1μm.

Tiny sponges are incorporated in specific dosage form and circulate around the body until they encounter the specific target site and stick on the surface and began to release the drug in a controlled and predictable manner. Owing to their small size and porous nature they can bind poorly- soluble drugs within the matrix which leads to improve their solubility and the bioavailability of poorly soluble drugs¹. Nanasponges are able to load both hydrophilic and hydrophobic drug molecules. The nanosponges are solid in nature and can be formulated as Oral, Parenteral, Topical or Inhalation dosage forms. For the oral administration, the Complexes may be dispersed in a matrix of excipients, diluents, lubricants and anticaking agents suitable for the preparation of capsules or tablets. Stability of these formulations over a wide range of pH in GI fluids and for higher temperatures upto 130°C makes these systems compatible with most vehicles and ingredients. Reduction in dosing and improve patient compliance, increases the bioavailability and enhanced formulation flexibility features this technology².

Hyperlipidemia is a condition when abnormally high levels of lipids i.e. the fatty substances are found in the blood. Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis related conditions like coronary heart disease (CHD), ischemic cerebrovascular disease, peripheral vascular disease and pancreatitis. It is initiated by lipid retention, oxidation, and modification, which provoke chronic inflammation, ultimately causing thrombosis or stenosis³.

Lovastatin belongs to the class of statins, and a class II drug according to Biopharmaceutical Classification System (BCS), used for lowering cholesterol (hypolipidemic agent). It binds to 3-hydroxy-3-methylglutaryl-coenzym A (HMG-CoA) reductase enzyme and inhibits the formation of cholesterol. Lovastatin is rapidly absorbed after oral administration, time to peak serum concentration is 2-4 hours and half-life is 2-4 hrs. It is available as conventional and extended release tablets but its exhibits poor oral bioavailability (<5%) because of its low solubility (0.0004mg/mL in water) and/or extensive metabolism in the gut and liver. Hence, the present investigation, we formulated lovastatin Nanosponges to enhance the solubility and dissolution characteristics of a poorly soluble drug of Lovastatin using nanosponges technology^4,5.

MATERIALS AND METHODS:

Materials:

Lovastatin (LOV) and Ethyl Cellulose were provided as a gift sample by Microlab Pvt Ltd., Hosur, India. Eudragit RS 100 was a kind gift from Evonik India Pvt, Ltd., Mumbai. Poly Vinyl Alcohol was a kind gift from Green moon biochem, Chennai, India. Dichloromethane, Methanol, Potassium dihydrogen phosphate and Sodium hydroxide were purchased from Micro Fine chemicals, Chennai, India. All other ingredients used were of analytical grade.

Methods:

Formulation of Lovastatin Nanosponges:

Lovastatin Nanosponges were prepared by Emulsion solvent evaporation method using two different polymers like Eudragit RS 100 and Ethyl cellulose at different drug to polymer ratios (1:1, 1:2, 1:3, 1:4, and 1:5). Polyvinyl alcohol as surfactant and dichloromethane as crosslinker as well as solvent. The Drug was dissolved in the required solvent (Dichloromethane) and the Polymers (1:1, 1:2, 1:3, 1:4, and 1:5) was dissolved in 20 ml of Dichloromethane. The Drug solution was poured into the polymer solution and the mixture was shaken well. Then the Drug polymer mixture was poured into the aqueous phase, Polyvinyl alcohol in Distilled water was used as the aqueous phase and the mixture was subjected to homogenization using high speed homogenizer at 1500 rpm for 2 hours at room temperature. The formed Nanosponges were centrifuged by high speed cooling centrifuge and the residue was freeze dried and packed in vials⁶.

PREFORMULATION STUDIES

Chemical compatibility study⁷

FTIR was used to find whether any kind of interaction between drug and polymer. The spectrum was recorded in the wave number region of 4000 to 400 cm^-1. The procedure consists of dispersing the sample (drug alone, Mixture of drug and excipients and the optimized formulation) in potassium bromide and compressed into discs by applying a hydraulic pressure. The pellet was placed in light path and spectrum was recorded.

Standard curve for Lovastatin⁸

100 mg of Lovastatin was weighed and transferred to 100 ml of volumetric flask. The drug was dissolved in 20 ml of methanol and volume was made up to 100 ml using phosphate buffer pH 6.8 to obtain a stock solution of 1000 µg/ml (stock solution I). 10 ml of this stock solution was again diluted with phosphate buffer pH 6.8 up to 100 ml to obtain a solution of 100 µg/ml (Stock solution II). From stock solution II 2,4,6,8 10 ml were transferred to series of 100 ml volumetric flasks. The volume was made up with phosphate buffer pH 6.8. The absorbance of these solutions was measured at 238 nm against blank.

Table 1: Formulation table of Lovastatin Nanosponges

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10
Drug: polymer ratio	1:1	1:2	1:3	1:4	1:5	1:1	1:2	1:3	1:4	1:5
Lovastatin (g)	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5
Eudragit RS 100 (g)	0.5	1	1.5	2	2.5	-	-	-	-	-
Ethyl cellulose (g)	-	-	-	-	-	0.5	1	1.5	2	2.5
Polyvinyl alcohol (g)	1	1	1	1	1	1.5	1.5	1.5	1.5	1.5
Dichloromethane(ml)	20	20	20	20	20	20	20	20	20	20
Distilled water (ml)	100	100	100	100	100	100	100	100	100	100

Solubility studies of pure Lovastatin⁹

Solubility of Lovastatin pure drug was tested in distilled water and phosphate buffer pH 6.8. An excess amount of Lovastatin pure drug was added in 20 ml of the pertinent media. The mixtures were stirred in a mechanical shaker at speed of 50 rpm for 24 hours and the temperature was maintained at 37±0.5⁰C. Visual inspection was carefully made to ensure there were excess lovastatin solids in the mixture, indicating saturation had been reached. Then the mixtures were filtered using 0.45μm micropore filter and filtrates were suitably diluted with same media. The absorbance of the solution was measured at 238nm in UV-Visible spectrophotometer.

EVALUATION OF LOVASTATIN LOADED NANOSPONGES:

Production yield^{2, 10}

Percentage yield can be determined by calculating the initial weight of raw materials and the finally obtained weight of Nanosponges. Percentage yield can be calculated by using the formula.

Practical mass of Nansponges

Production yield = ------------------------------------------------ X 100

Theoretical mass (drug+polymer)

Drug entrapment efficiency⁸

The drug entrapment efficiency of Nanosponges was determined spectrophotometrically (λ_max=238 nm). A sample of Lovastatin Nanosponge was mixed in methanol and made upto 100 ml with phosphate buffer (pH 6.8) and kept it for overnight. The drug content was determined and expressed as actual drug content in Nanosponges. The percentage entrapment efficiency (%EE) is calculated by following formula:

Percentage Actual drug content in Nanosponges

entrapment = ------------------------------------------------- X 100

efficiency Theoretical drug content

Solubility Studies of Lovastatin NSs¹⁰

Solubility of Lovastatin Nanosponges was tested in distilled water and phosphate buffer pH 6.8.

In vitro drug release studies¹¹

The in vitro release of Lovastatin from Nanosponges was evaluated using USP Type-II (Paddle) dissolution test apparatus. Lovastatin Nanosponges were filled in capsule and placed in a dissolution jar containing 900ml of Phosphate buffer pH 6.8 as dissolution medium maintained at 37±0.5⁰C and rotated at 50 rpm. 10 ml of samples were withdrawn at predetermined intervals upto 12 hrs and replaced with equal amount of phosphate buffer pH 6.8 for further dissolution testing. The absorbance was determined spectrophotometrically at 238nm.

Morphology of Nanosponges by Scanning Electron Microscopy^12,¹³

The Surface Morphology of the Nanosponges can be measured by SEM. Scanning electron microscopy was used to analyze particle size, shape and surface morphology of Nanosponges. The sample was mounted directly onto the SEM sample holder using double sided sticking tape and images were recorded at different magnifications at acceleration voltage of 10 kV using scanning electron microscope.

Particlesize and Polydispersity^14,15

Particlesize (z-average diameter) and polydispersity index (as a measure of particle size distribution) of Lovastatin loaded Nanosponge dispersion is performed by dynamic light scattering also known as photon correlation spectroscopy (PCS) using a Malvern Zetasizer 3000 Nano S (Malvern instruments, UK) at 25°C.

Zeta potential^13,16

The ZP is a determinant of the electric charge on the surface of the particles. The physical stability of colloidal systems is indicated by ZP values. The ZP values were assessed by determining surface charge on the Lovastatin Nanosponges using Malvern Zetasizer. 1ml of sample of Lovastatin suspension was filled in clear disposable zeta cell, without air bubble within the sample, the system was set at 25°C temperature and results recorded.

PREFORMULATION STUDY OF OPTIMIZED NANOSPONGES:l

Flow property measurements:

The flow properties are critical for an efficient capsule filling operation. A good flow of the powder or granules is necessary to assure efficient mixing and acceptable weight uniformity for the compressed tablets and capsules. The flow properties and porosity of Nanosponges are determined. The flow property measurements include bulk density, tapped density, angle of repose, compressibility index and Hausner’s ratio¹⁷.

OPTIMIZED NANOSPONGES FILLED IN HARD GELATIN CAPSULES:

The optimized Lovastatin loaded Nanosponges were filled into hard gelatin capsule each containing 40 mg of Lovastatin^18,19.

EVALUATION OF CAPSULES:

Uniformity of weight¹⁸

Intact capsule were weighed. The capsules were opened without losing any part of the shell and contents were removed as completely as possible. The shell was washed with ether and the shell allowed to stand until the odour of the solvent was no longer detectable. The empty shell was weighed. The average weight was determined. Not more than two of the individual weights deviate from the average weight by more than the percentage deviation and none deviates by more than twice that percentage.

Drug content²⁰

Five capsules were selected randomly and the average weight was calculated. An amount of powder was equivalent to 40 mg of Lovastatin was made upto 100 ml with phosphate buffer pH 6.8. It was kept overnight. 1 ml of solution was diluted to 50 ml using phosphate buffer pH 6.8 in separate standard flask. The absorbance of solution was recorded at 238 nm.

RELEASE KINETICS OF THE OPTIMIZED FORMULATIONS^21,²²

To study the in vitro release kinetics of the optimized formulation, data obtained from dissolution study were plotted in various kinetics models. Different kinetic models such as zero order (cumulative amount of drug released vs. time), first order (log cumulative percentage of drug remaining vs. time), Higuchi model (cumulative percentage of drug released vs. square root of time), Korsmeyer-Peppas model (Log Cumulative percent drug release versus log time) and Hixson Crowell model (cube root of cumulative percentage of drug remaining vs. time) were applied to interpret the drug release kinetics from the formulations. Based on the highest regression values for correlation coefficients for formulations, the best‐fit model was decided.

STABILITY STUDIES²³

Stability studies were carried out as per ICH guidelines. The optimized Lovastatin Nanosponges formulations were placed in airtight screw cap, amber coloured vials and kept under accelerated conditions (temperature 40°C±2°C and RH 75±5%) using stability chamber and refrigerated temperature (4±2⁰C) for the period of 3 month. The samples were withdrawn at predetermined intervals and evaluated for their physical appearance, entrapment efficiency, drug content and in vitro drug release.

RESULT AND DISCUSSION

FORMULATIONOF LOVASTATIN LOADED NANOSPONGES

Fig. 1: LOV NSs before Lyophilization

Fig. 2: LOV NSs after Lyophilization

PRE-FORMULATION STUDIES:

Chemical compatibility study: FT-IR spectroscopic studies:

Drug and excipient compatibility was confirmed by comparing FT-IR spectrum of pure drug with that of various excipients used in the formulation. The characteristic absorption peaks of drug and excipients were obtained as shown in above. It shows no shift and no disappearance of characteristic peaks of drug. This suggests that there is no interaction between the drug and excipients used in the formulation.

Standard calibration curve of Lovastatin:

Standard solutions of different concentrations (Table 2) were made and their absorbance was recorded at 238 nm for Lovastatin. Drug concentrations versus absorbance curve were plotted as given in Figure3.

Table 2: Calibration curve data of LOV

Concentration (µg/ml)	Absorbance
0	0
2	0.1153±0.002065
4	02308±0.005142
6	0.3544±0.006825
8	0.4786±0.006243
10	0.6020±0.007253
12	0.7200±0.012972

Mean ±SD (n= 3)

Figure 3: Calibration Curve of Lovastatin

The linearity was found to be in the range of 2- 12μg/ml. The regression value was closer to 1 indicating the method obeyed Beer-lambert’s law.

Solubility studies of Lovastatin:

Solubility of Lovastatin pure drug in distilled water and phosphate buffer pH 6.8 was studied. It was found to be 0.00021116mg/ml in distilled water and 0.00352055 mg/ml in Phosphate buffer pH 6.8. Lovastatin pure drug in distilled water and phosphate buffer pH 6.8 was found to be insoluble.

Evaluation of Lovastatin Loaded Nanosponges:

Percentage yield:

The percentage yield of Nanosponges was calculated and the values are given in the table 3. The production yield of all formulations was observed in the range of 85.83 to 99.85%. It was found that increase in the drug: polymer ratio resulted in increased production yield but after certain concentration it was observed that as the ratio of drug to polymer was increased, the production yield decreased.

Drug entrapment efficiency:

Table 3: Percentage yield and Entrapment Efficiency

F. Code	Percentage Yield (%)	Entrapment Efficiency (%)
F1	99.10	79.48±0.070711
F2	99.33	83.73±0.438406
F3	99.85	91.18±0.148492
F4	98.40	90.87±0.735391
F5	99.66	82.28±0.438406
F6	95.50	81.25±0.438406
F7	96.66	83.005±0.289914
F8	98.05	90.04±0.289914
F9	99.60	74.57±1.096016
F10	85.83	61.68±0.586899

The entrapment efficiency of the Lovastatin formulations was determined and the values are given in the table 3. Entrapment efficiency of all the formulations was observed to be between 61.68% and 91.18%. The results show that the increase in polymer concentration increased the drug entrapment efficiency. This may be due to higher concentration of the polymer would have provide more space and also reduced escaping of drug into the external phase. But after certain concentration it was observed that the increasing the concentration of the polymer, entrapment efficiency decreased. The entrapment efficiency was changed when drug and polymer ratio has been changed. The entrapment efficiency was found to be higher in F3 (91.18%) and F8 (90.04%) comparatively with other formulations.

Solubility studies of Lovastatin Nanosponge

Table 4: Solubility of Nanosponges in various media

F. code	Solubility in distilled water (mg/ml)	Solubility in Phosphate buffer pH 6.8 (mg/ml)
Pure drug	0.0002116	0.00352
F1	1.34125	2.17768
F2	1.47379	2.26049
F3	1.95408	2.98923
F4	1.85472	2.40122
F5	1.34125	2.04519
F6	1.13427	2.16112
F7	1.13827	2.26049
F8	1.92925	2.87329
F9	1.68082	2.236
F10	1.29161	1.95409

Solubility of Nanosponges in distilled water and phosphate buffer pH 6.8.were studied and the values are given in table 4. The solubility of all formulations in distilled water and Phosphate buffer pH 6.8 were found to be in the range of 1.29161 to 1.95408mg/ml and 1.95409 to 2.98923mg/ml respectively. The solubility of all formulation improved (from insoluble to slightly soluble) compared to pure drug of Lovastatin. The solubility of formulations F3 and F8 in distilled water and Phosphate buffer pH 6.8 were improved (9234 and849 fold) and (9117and 816 fold) respectively.

In vitro drug release

The drug release (Table-5) rate was related to drug: polymer ratio. It was observed that the drug release rate decreased with an increase in the concentration of polymer. This may be due to the fact that the release of drug from the polymer matrix takes place after complete swelling of the polymer and as the concentration of polymer in the formulation increases the time required to swell also increases.

Table 5: in vitro drug release for all formulations

Time (hrs.)	Cumulative percentage drug release
Time (hrs.)	Pure drug	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10
1	7.67	20.12	20.01	16.70	7.69	4.72	22.92	19.60	17.41	11.41	7.67
2	20.24	36.42	33.54	24.01	18.20	12.24	36.40	31.54	26.13	21.59	13.01
3	50.89	44.83	44.90	34.05	26.30	22.30	48.49	46.03	33.51	31.67	21.74
4	55.32	60.26	52.18	41.06	35.20	28.47	58.57	50.34	43.10	42.64	27.15
5	-	67.76	59.46	50.36	41.16	35.55	65.22	64.27	52.27	47.55	36.33
6	-	74.70	67.33	57.37	45.41	38.84	73.64	72.36	59.76	53.24	41.66
7	-	87.48	76.47	64.12	51.60	45.39	86.31	82.10	67.19	57.51	47.62
8	-	95.09	87.31	72.14	58.39	53.45	98.15	92.63	74.08	64.33	55.17
9	-	-	97.02	78.81	66.80	58.70	-	96.60	80.63	72.03	58.76
10	-	-	-	88.21	71.17	64.54	-	97.57	87.64	77.86	68.70
11	-	-	-	93.97	79.19	70.57	-	-	94.54	88.90	73.11
12	-	-	-	98.15	85.74	79.29	-	-	97.57	89.55	76.89

In vitro release of optimized formulation showed a rapid initial burst, followed by a very slow drug release. An initial, fast release may be due to more amount of the drug was entrapped near the surface of the NSs due to larger surface area, rather than inside the particles.

Figure 4: In vitro release study of Nanosponges (F1-F0)

By comparing the above dissolution studies it was clearly observed thatthe drug was released upto 98.15% at the end of 12 hours by F3 and F8 formulation, so it was taken as the optimized formulation.

Based on the entrapment efficiency and in vitro drug release F3 and F8 was selected as optimized formulations. These optimized formulations (F3 and F8) characterized for surface morphology, particle size analysis, zeta potential and FTIR analysis.

Scanning Electron Microscope (SEM) analysis

Figure 5: SEM image of optimized formulation F3

Figure 6: SEM image of optimized formulation F8

SEM analysis shows that the Nanosponges were spherical with numerous pores on their surface, uniform and spongy in nature. The pores are tunneled inwards which may be due to diffusion of solvent (Dichloromethane) from the surface of the Nanosponges.

Determination of particle size and polydispersity

Particle size and polydispersity was determined by malvern particle size analyzer and the value given in table 6. This is within nanometric range and uniformity of particle size within formulation.

Table 6: Particle size, Polydispersity and Zeta potential

F. code	Particle size (nm)	Polydispersity	Zeta potential (mV)
F3	727.0	0.404	-21.3
F8	769.5	0.155	-21.6

Zeta potential

The zeta potential was determined by zeta sizer and the value given in table 6. It shows that the formulation is stable.

PREFORMULATION STUDIES OF OPTIMIZEDNANOSPONGES

Table 7: Preformulation studies of the pure drug and optimized formulation

F. Code	Bulk density (g/ml)	Tapped density (g/ml)	Carr’s Index (%)	Hausner’s ratio	Angle of repose (θ)	Porosity (%)
Pure drug	0.306±0.017	0.460±0.038	33.38±1.9	1.501±0.04	48.23±1.26	44.27±0.29
F3	0.274±0.004	0.307±0.010	10.69±1.9	1.119±0.02	28.19±1.48	73.39±0.15
F8	0.161±0.002	0.185±0.003	12.85±1.4	1.147±1.42	30.03±2.90	81.45±0.28

Mean ±SD (n= 3)

The optimized formulations F3 and F8 have good flow property compared with pure drug. Pure drug have very poor flow.

OPTIMIZED LOVASTATIN NSs FILLED IN THE CAPSULES

The optimized Nanosponges were filled into “0” size hard gelatin capsules without adding glidant or exicipients because of good flow properties. The filled capsule contains 40mg of Lovastatin.

POST FORMULATION STUDIES FOR CAPSULES

Table 8: Uniformity of Weight for contents in capsules

Formulation Code	Average weight of capsule (g)
C-F3	0.1806±0.001779
C-F8	0.1753±0.000527

The Capsules comply with the official test for Uniformity of weight.

Table 9: Drug Content for Capsules

Formulation code	Drug content (%)
C-F3	99.32±0.233345
C-F8	97.64±0.374767

Mean ±SD (n= 3)

The drug content was within the limits (not less than 90% and not more than 110%). It complies with the official standard.

RELEASE KINETICS OF OPTIMIZED FORMULATIONS

The data from in vitro release of optimized formulations F3 and F8 were fit into various kinetic models to find out the mechanism of drug release from Lovastatin Nanosponges. A good linearity was observed with the zero order (R²=00.9905 and 0.9853), the zero order kinetics explains the controlled release of the prepared Nanosponges over the period of 12 hours. Higuchi plot (R²=0.9628 and 0.9704) show linearity, which indicates the rate of drug release through the mode of diffusion and to further confirm the diffusion mechanism, data was fitted into the Korsmeyer Peppas equation which showed linearity. The slope of the Korsmeyer Peppas plot (n= 0.743 and 0.802) was found to be more than 0.5 indicating the diffusion was anomalous diffusion (Non Fickian diffusion). Thus, the release kinetics of the optimized formulation was best fitted into Higuchi model and showed zero order drug release with anomalous diffusion (Non Fickian diffusion) mechanism.

Table 10: R²Values of various Kinetic Models

Kinetic Models	Coefficient of determination (R²)
Kinetic Models	F3	F8
Zero order	0.9905	0.9853
First order	0.8407	0.8768
Higuchi	0.9628	0.9704
Korsmeyer and Peppas	0.9951	0.9975
Hixson crowell	0.9488	0.9652

STABILITY STUDIES

The optimized formulations subjected to stability studies as per ICH guidelines. The results are shown in table 11and 12.

Table 11: Stability data for Optimized Formulation

Stability condition		Physical appearance			Entrapment Efficiency (%)			Drug content (% w/w)
Stability condition		Initial	After 45 days	After 90 days	Initial	After 45 days	After 90 days	Initial	After 45 days	After 90 days
40±2^oC /75±5%RH	F3	NC	NC	NC	91.18	90.67	88.97	99.32	99.12	98.43
40±2^oC /75±5%RH	F8	NC	NC	NC	90.04	89.63	88.08	97.64	97.31	95.97
4±2^oC	F3	NC	NC	NC	91.18	91.10	90.21	99.32	99.31	98.42
4±2^oC	F8	NC	NC	NC	90.04	89.94	89.18	97.64	97.34	96.14

Table 12: Stability data for Optimized Formulation (Cumulative % drug release)

Time (hrs)	Cumulative % drug release
	40±2^oC/75±5%RH						4±2^oC
	F3			F8			F3		F8
	Initial	After 45 days	After 90 days	Initial	After 45 days	After 90 days	After 45 days	After 90 days	After 45 days	After 90 days
1	16.70	15.26	14.98	17.41	16.21	16.05	16.12	15.75	17.22	16.66
2	24.01	24.04	23.70	26.13	25.78	24.90	23.69	22.92	26.16	25.75
3	34.05	32.97	32.29	33.51	33.11	32.13	34.13	33.53	32.96	32.15
4	41.06	40.27	40.05	43.10	41.83	41.25	42.11	41.50	42.77	43.81
5	50.36	50.06	49.62	52.27	51.73	51.60	51.29	49.83	51.96	51.07
6	57.37	55.93	56.12	59.76	59.05	58.34	56.75	58.07	59.08	58.76
7	64.12	62.94	62.31	67.19	65.84	65.12	65.07	63.54	66.98	66.91
8	72.14	71.11	70.93	74.08	72.93	72.09	71.15	70.74	74.22	73.66
9	78.81	77.36	76.96	80.63	79.26	78.62	78.69	79.09	81.10	78.73
10	88.21	86.93	86.77	87.64	86.73	86.16	87.72	89.04	88.22	86.34
11	93.97	92.21	91.97	94.54	92.41	92.11	93.08	92.90	93.45	93.27
12	98.15	97.25	96.05	97.57	96.09	95.09	98.07	97.05	97.11	96.16

No significant changes in Physical appearance, entrapment efficiency, drug content and in vitro drug release at storage condition of 40°C ± 2°C / 75 ± 5% RH and 4±2^oC after the end of 0, 45 days and 90 days.

CONCLUSION:

Lovastatin is a poorly soluble drug with a short half-life, thus selected as a model drug for Nanosonges drug delivery system. The present study demonstrated Nanosponges prepared with eudragit RS 100 and ethyl cellulose successfully filled into capsules for oral administration. Such formulation act by enhancing the solubility of Lovastatin and releases the drug in a controlled manner for an extended period of time lead to reduce dose dependent side effects, improve the patient compliance and bioavailability. The foregoing results attempt to suggest that for highly lipophilic drugs like Lovastatin, Nanosponge approach would be a possible alternative delivery system to conventional oral formulation to improve its bioavailability.

ACKNOWLEDGEMENT:

Authors are thankful to College of Pharmacy, Madras Medical College, for giving us the opportunity and providing required necessary facilities to carry out this work.

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Received on 03.05.2019 Modified on 17.01.2020

Research J. Pharm. and Tech 2021; 14(11):5653-5660.

DOI: 10.52711/0974-360X.2021.00983