Lovastatin Loaded Chitosan Nanoparticles: Preparation, Evaluation and  In vitro Release Studies


Anilkumar J. Shinde and Harinath N. More*

Department of Pharmaceutics, Bharati Vidyapeeth College of Pharmacy, Near Chitranagari, Kolhapur

Corresponding author: ajshinde70@rediffmail.com



The goal of the present investigation was to formulate and evaluate a potential of chitosan nanoparticles as carriers for the lovastatin drug. Lovastatin is a BCS class-II drugs having low solubility and high permeability. Since lovastatin undergoes extensive first pass extraction in the liver, the availability of the drug to the general circulation is low (< 5%). Nanoparticles were prepared by modified ionotropic gelation method using 3² full factorial design. From the preliminary trials, the constraints for independent variables X1 (concentration of chitosan) and X2 (concentration of sodium tripolyphosphate) have been fixed. Factors included concentration of chitosan and STPP, have been examined to investigate effect on particle size, encapsulation efficiency, zeta potential, % release, SEM, FTIR, XRD and DSC analysis of lovastatin. Release study was conducted by in vitro dialysis membrane method using phosphate buffer pH 7.4 at 37oC. The diameter of prepared nanoparticles was controlled in the range of 100 - 800nm. Experimental results showed that lovastatin encapsulation efficiency was decreasing with increasing chitosan concentration. The particle size is independent of encapsulation efficiency. Spectrograms of FTIR and DSC showed that lovastatin physically absorbed by chitosan matrix. SEM photographs demonstrated prepared nanoparticles were in spherical shape and narrow diameter distribution. In vitro drug release study of selected factorial formulations (CL1, CL4, CL7) showed, 87.42± 0.020 %, 85.72± 0.025%, and 78.88± 0.025% release respectively in 24 hrs. The Zeta potential of all the batches were in the range of + 30 mv and batch CL4 was found to be + 35.32 mv. So it conclude that prepared all formulation were good stability. The release profiles of all batches were very well fitted by both the zero order mode and the anomalous transport.  These results indicate that lovastatin nanoparticles could be effective in sustaining drug release for a prolonged period.


KEYWORDS: Chitosan, factorial design, Ionotropic gelation, Lovastatin, sustained release




One of the most attractive areas of research in drug delivery, today is the design of nanosystems that are able to deliver drugs to the right place, at appropriate times and at the right dosage. Nanoparticulate delivery systems, are the reduction of drug particle to the nano-scale, increases dissolution velocity and saturation solubility, have the potential power to improve drug stability, increase the duration of the therapeutic effect and permit administration through enteral or parenteral administration, which may prevent or minimize the drug degradation and metabolism as well as cellular efflux. Therapeutic effectiveness of a drug depends upon the bioavailability and ultimately upon the solubility of drug molecules. Solubility is one of the parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown.


Currently only 8% of new drug candidates have both high solubility and permeability.1,2 It has been estimated that roughly 40% of all investigational compounds fail development because of poor bioavailability that is often associated with aqueous insolubility.3 In the recent years, nanoparticle technology has emerged as a strategy to tackle such formulation problems associated with poorly water and lipid soluble drugs.4 5,6


Dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, or their combination, is a major risk factor for cardiovascular diseases. Generally, dyslipidemia is characterized by increased fasting concentrations of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), in conjunction with decreased concentrations of high-density lipoprotein cholesterol (HDL-C). At present, these lipid imbalances are most routinely treated with pharmacological therapy.7,8  However, many cholesterol lowering agents, like, simvastatin, lovastatin, atorvastatin are generally used. Lovastatin is a HMG Co-A reductase inhibitor, highly lipophilic but poorly water soluble drug belonging to the class statins, widely used for the treatment of hypercholesterolemia. The drug has a very short half life of 1.1-1.7 h with a very low bioavailability (< 5%).9,10 Chitosan is a natural cationic polysaccharide consisting of (1-4)-2-amino-2-deoxy-D-glucopyranosyl units. It breaks down slowing to harmless products (amino sugars), which are completely absorbed by the human body.11,12 Chitosan has been used as a nanoparticle material owing to its versatile biodegradability, biocompatibility, and natural origin. Biodegradable nanoparticulate systems have received considerable attention as potential drug delivery vehicles.13-17


The objective of the present study was to evaluate the possibility of chitosan nanoparticles as carriers for lovastatin. The challenge was to entrap a hydrophobic molecule into hydrophilic nanoparticles formed by the process of ionotropic gelation based on the interaction between the negative groups of the sodium tripolyphosphate (STPP) and the positively charged amino groups of chitosan. This gelation process is due to the formation of inter and intra cross-linkages between/within polymer chains, mediated by the poly anions.18,19 The cationic nature of chitosan has been conveniently exploited for the development of particulate drug delivery systems. More recently, chitosan NPs have been developed based on the ionotropic gelation of chitosan with sodium tripolyphosphate (STPP), for drug encapsulation, Calvo et al., 1997 20,21


The study was carried out to develop lovastatin nanoparticles in order to enhance solubility, dissolution and bioavailability by decreasing the particle size of the drug. So, as reduce the frequency of doses, toxicity and to improve the therapeutic efficacy. The formulated lovastatin nanoparticles evaluate their particle size, entrapment efficiency, drug release, Zeta potential, FTIR, DSC, SEM and stability studies.




Lovastatin was obtained gift sample from Aurobindo Pharmaceutical Ltd., Hydrabad; Chitosan was procured from Marine chemicals, Cochin, Sodium tripolyphosphate was purchased from Loba chemie, Mumbai, Dialysis bag (cellophane membrane, molecular weight cut off 10000-12000 Da, purchased from Hi-Media, Mumbai. India. All other reagents and chemicals used in this study were of analytical Grade.


Preparation of Chitosan nanoparticles:

Chitosan nanoparticles containing lovastatin were prepared by modified ionotropic gelation method adapted.21 Chitosan was dissolved in 1% acetic acid solutions with sonicator to obtain clear solution and adjusted the pH 5-6 with 0.1N sodium hydroxide solution, while STPP was dissolved in deionized water. Lovastatin was dissolved in ethanol/ water mixture (1:1) to obtained clear solution. Lovastatin solution was added dropwise with syringe needle size 0.45 mm to 40 ml chitosan solution. The 20 ml of STTP solution was added dropwise 0.75ml/min. under magnetic stirring (1000 rpm) at ambient temperature. The formulation stirred for 30 minutes so as to remove ethanol content. All the formulations sonicated at fixed time at 30 minutes. All experiments were performed in triplicates. Nanoparticles were collected by centrifugation at 15,000 rpm for a period of 1 h and supernatants were discarded. Followed by freeze drying, nanoparticles were collected. 22


Experimental Design:

The formulations were fabricated according to a 3² full factorial design, allowing the simultaneous evaluation of two formulation variables and their interaction. The experimental designs with corresponding formulations are shown in table no.1.and 2. The dependent variables that were selected for study particle size (Y1) and % drug entrapment (Y2).


Characterization of the Nanoparticles

Determination of particle size:

The particle size and size distribution of the lovastatin loaded chitosan nanoparticles were characterized by photon correlation spectroscopy (PCS) using a Zetasizer 2000 Malvern Instruments, UK, at a scattering angle of 90º23 Nanosuspension was diluted with filtered (0.22μm) ultra pure water and analysed using Zeta sizer. This analysis yields the mean diameter (z-average, measuring range: 20–1000 nm), which allows sample measurement in the range of 0.020-2000.00 μm.


Table-1: Experimental design and Parameters for 3² Full Factorial Design  Batches

Batch code

Variables level in coded Form

Particle Size

( nm)

% Drug entrapment

± SD*

% Free Drug

± SD*

Polydisperslity index







98.52 ± 0.030

1.488 ± 0.030






98.38 ± 0.025

1.620 ± 0.035






98.32 ± 0.037

1.680 ± 0.015






96.85 ± 0.035

3.150 ± 0.020






96.51 ± 0.040

3.490 ± 0.040






96.19 ± 0.030

3.810 ± 0.036






94.47± 0.015

5.530 ± 0.030






94.10 ± 0.036

5.900 ±0.023






94.03 ± 0.025

5.965 ± 0.034


*SD indicates standard deviation n=3

Table No 2: Translation of coded levels to actual quantities

Coded Levels




Drug: Polymer ratios  (X1)*





(X2) in %*





Polydispersity index:

Polydispersity was determined according to the equation 1.


                                       D (0.9)-D (0.1)

Polydispersity index = ------------------ × 100      ….1

                                             D (0.5)

Where, D (0.9) corresponds to particle size immediately above 90% of the sample.

D (0.5) corresponds to particle size immediately above 50% of the sample.

D (0.1) corresponds to particle size immediately above 10% of the sample


Determination of entrapment efficiency:

The encapsulation efficiency of nanoparticles was determined by first separating the nanoparticles formed from the aqueous medium by centrifugation at 15000 rpm for 30 min. The amount of free lovastatin in the supernatant was measured by UV spectrophotometery at 243 nm (Shimadzu UV-1700,) after suitable dilution. The lovastatin entrapped in the nanoparticles was calculated as Eq 2.


                                            ( Tp –Tf  )

Drug Entrapment (%) = ---------------- × 100        ….2


where Tp is the total lovastatin used to prepare the nanoparticles and Tf is the free lovastatin in the supernant.


Determination of zeta potential:

The zeta potential of the drug-loaded chitosan nanoparticles was measured on a zetasizer (Malvern Instruments) by determining the electrophoretic mobility in a microelectrophoresis flow cell.24 All the samples were measured in water at 25 ºC in triplicate.


Statistical Analysis::

The results from factorial design were evaluated using PCP Disso 2000 V3 software. Step wise backward linear regression analysis was used to develop polynomial equations for dependent variables particle size (Y1) and % drug entrapment (Y2) which form of equation-1:


Y= β0 + β1X1 + β2X2 + β11X12 + β22X22 + β12X1X2 +  ε  …    1


Where Y is estimate response of dependent variable, β0 arithmetic mean response of nine batches, and β1 estimated coefficient for factor X1. The main effects (X1 and X2) represent average result of changing one factor at a time from its low to high value. The interaction term (X1X2) shows how the response changes, when two factors are simultaneously changed. The polynomial terms (X12 and  X22 ) are included to investigate non-linearity. ε is the random error. The simplified models were then utilized to produce three dimensional response surface plots to analyze the influence of independent variables.

In vitro drug release study:

The lovastatin loaded chitosan nanoparticles, after separation by centrifugation, were re-dispersed in 5mL phosphate buffer solution pH 7.4, placed in a dialysis membrane bag, tied and immersed in 150mL of PBS in a 250ml beaker. The entire system was stirred continuously at 37ºC with a magnetic stirrer at 100 rpm. Required quantity 5ml of the medium was withdrawn at specific time periods (1, 2, 3, 4, 6, 8, 10, 12, 24 hours) and same volume of dissolution medium was replaced in the flask to maintain a constant volume. The withdrawn samples were filtered through a filter paper (0.22 μm, Whatman Inc., USA) and 5 ml filtrate was made up to volume with 100 ml of Phosphate buffer pH 7.4. The samples were analyzed for drug release by measuring the absorbance at 243 nm using UV-visible spectrophotometer and calculate percent cumulative release of Lovastatin.25


Fourier Transform Infrared Spectroscopy study:

Infrared spectrum of lovastatin, nanoparticle formulation was determined by using Fourier Transform Infrared Spectrophotometer (FTIR-4100, Shimadzu) using KBr dispersion method. The base line correction was done using dried potassium bromide. Then the spectrum of dried mixture of drug and potassium bromide was run.


Differential scanning calorimetry study:

Differential scanning calorimetry (DSC) is one of the most powerful analytical techniques, which offers the possibility of detecting chemical interaction of lovastatin and chitosan nanoparticles. DSC measurements were carried out on a modulated DSC Instrument: SDT Q600 V20.9 Build 20 equipped with a thermal analysis data system (TA instrument). Samples of 2–10 mg were placed in aluminium pans and sealed. The probes were heated from 25 to 250ºC at a rate of 10 K/min under nitrogen atmosphere.


X-ray Diffraction Study:

X-ray diffraction analysis was employed to detect the crystallinity of the pure drug and the nanoparticle formulation, which was conducted using a  Philips PW 3710 x-ray diffractometer (XRD) with a copper target and nickel filter (Philips Electronic Inst, Holland). Powders were mounted on aluminium stages with glass bottoms and smoothed to a level surface. The XRD pattern of each sample was measured from 10 to 50 degrees 2-theta using a step increment of 0.1 - 2- theta degrees and a dwell time of 1 second at each step.


Scanning electron microscopy study:

The morphology of nanoparticles was examined by using scanning electron microscopy (SEM, JSM-6360LV scanning microscope Tokyo, Japan). The nanoparticles were mounted on metal stubs using double-sided tape and coated with a 150 Å layer of gold under vacuum. Stubs were visualized under scanning electron microscope. SEM has been used to determine particle size distribution, surface topography, texture and examine the morphology of fractured or sectioned surface. The same generally used for generating three dimensional surface relief images derived from secondary electrons. The examination of surface of polymeric drug delivery system.


Stability of nanoparticles:

The formulation of nanoparticles were separated into three portions one portion was kept at room temperature, second at 45oC, and third at 4oC for one month. At weakly intervals samples were determined spectrophotometrically at 243 nm using phosphate buffer pH 7.4 and drug content were estimated.




The Nanoparticles were prepared by Modified Inotropic gelation method by using chitosan as polymer and STTP as cross linking agent. The particle sizes were evaluated by Malvern metasizer ranging from 100 nm to 800 nm. The entrapment efficiency of the drug was decreased by increasing the load of polymer. Batch CL1,1:1 ratio of drug and polymer has highest percentage of entrapment efficiency i.e 98.52%. The cumulative percentage of drug release from lovastatin nanoparticles after 24th hour 87.42± 0.020 %, 85.72± 0.025%, and 78.88± 0.025% respectively for CL1, CL4, CL7.  In stability studies there were no changes in the drug content in room temperature and 4oC, which was suitable for the storage condition. From all the above results the lovastatin nanoparticles with 1:3 ratio of drug, polymer showed significant sustained release. The most satisfactory nanoparticles were obtained at chitosan concentration of 0.20 %w/v and sodium tripolyphosphate concentration of 0.10 %w/v.


Drug entrapment studies:

The percentage encapsulation efficiency shown in table 1.and fig.1.  Microncapsulation efficiency of CL1 formulation nanoparticles  98.52%, CL4 formulation nanoparticles 96.85 %, CL7 formulation nanoparticles 94.47%. This variation due to the chitosan concentration, when increasing the chitosan concentration decrease the encapsulation efficiency due to increase the viscosity of chitosan hindered the drug encapsulation efficiency. Ionic interaction between the polymer and drug may lead to increase entrapment of the drug in nanoparticles.


Fig. 1. % Entrapment efficiency of formulations CL1-CL9.

Zeta potential, particle size, and polydispersity Index:

As table 1 shows, the size of the nanoparticles increased after increasing the polymer concentration, while zeta potential was unchanged. Zeta potential was in the range of 25 - 32 mV for all formulations, shown in fig .4., while polydispersity index was less than 0.9, shown table 1. which indicates homogeneous nature of the formulation. Sonication for 20 min reduced particle size to nano level; thereafter, there was no further change in particle size. Although the particles fell within nanosize range (100 – 800 nm) shown in fig.2 and table 1.  It seems that the relatively lower viscosity of chitosan with a concentration (0.1%) and an appropriate concentration of STPP (0.1 %w/v), particle size of CL1 batch was show lower i.e.137 nm and chitosan concentration (0.2 %) and concentration of STPP (0.1 %w/v) promoted the formation of nanoparticles at lower size of CL4 batch i.e 292 nm. shown in fig. 2 and fig.3.


Fig. 2. Particle size of the formulations CL1-CL9.


Fig. 3. Particle size of the formulation CL4 batch ( 292 nm)


Fig. 4. Zeta potential of  formulation CL4 batch ( 35.32 Mv)


In vitro drug Release Study:

In vitro drug release study conducted according to highest % drug entrapment and lowest particle size, batches CL1, CL4 and CL7 were selected, shown in table 3.and fig 5. Drug release from nanoparticles and subsequent biodegradation are important for developing successful formulations. The release rate of nanoparticles by diffusion and biodegradation process.  The drug release follows zero order release kinetics with anomalous transport mechanism shown in table 4. Drug release for selected factorial formulations CL1, CL4, and CL7 are 11.10 ± 0.010 % , 11.01± 0.025% and 10.78± 0.032 % respectively, after 1 hr. These formulation show initial burst release followed by a controlled release. Finally, it can be concluded that the different drug release rates may be attributed to different sizes of the nanoparticles. It is expected as the particle size of chitosan nanoparticle is smaller, their surface area will be more and the drug release is faster.


Fig. No. 5. Cumulative % release of formulations CL1,CL4 and CL7

Table 3.  Percent cumulative In vitro drug release study


in hrs.

Cumulative % release

mean ± *SD, n = 3





11.10 ±  0.010

11.01± 0.025

10.78± 0.032


16.30± 0.020

16.00± 0.020

15.47± 0.020


15.10± 0.015

14.36± 0.015

13.82± 0.026


16.87± 0.025

16.58± 0.025

16.15± 0.025


18.83± 0.0264

17.81± 0.020

16.98± 0.015


32.41± 0.056

31.71± 0.026

30.41± 0.020


48.43± 0.015

45.62± 0.015

43.98± 0.030


60.81± 0.025

58.20± 0.020

57.52± 0.026


67.84± 0.015

63.08± 0.015

61.37± 0.015


87.42± 0.020

85.72± 0.025

78.88± 0.025

*SD indicates standard deviation n=3


Table 4 : Model fitting of batches CL1 – CL9

Batch code

Model fit



Peppas koresmeyer



Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Zero order



Anomalous transport


Development of Polynomial Equations:

The experimental design and Parameters in table 1and 2 for factorial formulations, CL1 to CL9 polynomial equations for two dependent variables, particle size and % drug entrapment have been derived using PCP Disso 2000V3 software.

The equation derived for particle size is:

Y1 =  592.70 +  86.025X1 +  175.00 X2 + 96.025X12  …     2


The equation derived for % drug entrapment is:

Y2 =  535.65 -25.76X1 +99.00X2 + 111.23X12 + 31.52 X22 + 1757 X1X2….   3


In equations no. 2 positive sign for coefficient of X2 indicates that the particle size of nanoparticles increases, when concentration of stabilizer STPP is increased and positive sign for coefficient of X1 indicate positive effect of concentration chitosan on particle size. In equation no.3, negative sign for coefficient of X1 indicates that the % drug entrapment deceases, when concentration of chitosan increases and positive sign for coefficient of X2 indicates that % drug entrapment of nanoparticles decreases, when concentration of stabilizer STPP increases. The closeness of predicted and observed values for particle size and % drug entrapment indicates validity of derived equations for dependent variables.


Response Surface Plots:

The response surface plots of particle size and % drug entrapment are shown in fig. no. 6 and 7 respectively. The response surface plots illustrated that as concentration of chitosan increases, the value of dependent variable, particle size increases and as concentration of STPP increases the value of dependent variable, particle size increases. Similarly the response surface plots for % drug entrapment shows negative effects of independent variable, chitosan concentration increases the % drug entrapment was deceased and as concentration of STPP increases the % drug entrapment was also decreased.


Fig. 6: Response surface plot showing effect of factorial variables on particle size.


Fig.7. Response surface plot showing effect of factorial variables

on % drug entrapment


Fourier Transform Infrared Spectroscopy ( FTIR ) study:

F.T.I.R. study was carried out to confirm the compatibility between the selected polymer chitosan, drug lovastatin and nanoparticles, are presented in fig. 8. The spectra obtained from the I.R. studies are from 4000 cm-1 to 400cm-1. It was confirmed that there are no major shifting as well as no loss of functional peaks between the spectra of drug, polymer and drug loaded nanoparticles 3510 cm-1 (Alcohol O-H stretching vibration), 3016 cm-1 (Olefinic C-H stretching vibration), 1725 (Lactone and ester carbonyl strech) 1275, (Lactone and Ester C-O-C bending vibration), 972 cm-1 (Alcohol C-OH strech) respectively. Comply with peak of chitosan and lovastatin, indicate that lovastatin compatible with the chitosan and sodium tripolyphosphate.


Fig. 8 FTIR spectra of Chitosan (A), lovastatin (B) and formulation CL4) (C).


Differential Scanning Calorimetry (DSC) study:

Differential Scanning Calorimetry study gives information regarding the physical properties like crystalline or amorphous nature of the samples. The DSC thermogram of  lovastatin shows an exothermic peak at 143.99 ºC corresponding to its melting temperature. However no sharp endotherm was seen at 149°C for the DSC curves of the lovastatin nanoparticles in fig. 9. This shows the crystallinity of the drug has been reduced significantly in the nanoparticles. Hence it could be concluded that in both the prepared chitosan nanoparticles loaded drug was present in the amorphous phase and may have been homogeneously dispersed in the chitosan matrix.


Fig. 9. DSC thermogram of chitosan (A), lovastatin( B) and

Formulation(CL4) (C) .

X-ray Diffraction Study:

XRD pattern of the lovastatin, chitosan and selected nanoparticle formulation are shown in fig. 10. The nanoparticles prepared with chitosan was characterized by less intensity of the diffraction peak when compared to that of lovastatin. The diffraction spectrum of pure lovastatin showed that the drug was of crystalline nature as indicated by numerous, distinct peaks. Numerous prominent diffraction peaks of lovastatin were observed indicating the presence of crystalline. This clearly indicates the reduction in the crystallanity of the precipitated lovastatin nanoparticles.


Fig.  10. XPRD spectra of chitosan(A, lovastatin(B) and formulation (CL4) (C).

Scanning electron microscopy (SEM) study:

The morphology of nanoparticles was examined by scanning electron microscopy (SEM, JSM-5310LV scanning microscope Tokyo, Japan.  The SEM images of pure drug particles and the nanoparticles are presented in  fig 11, and fig 12. While unprocessed lovastatin particles have appeared as irregular- shaped crystals, a drastic change in the morphology and shape of drug was observed for the nanoparticles prepared with chitosan concentration (0.2 %) and concentration of STPP (0.1 %w/v) promoted the formation of nanoparticles at spherical in shape and lower size of CL4 batch.


Stability studies:

The stability of the formulation during storage is of utmost important as it determines the shelf life of the formulations. The greater stability of formulation CL4 over CL1 and CL7 may be attributed to the facts that 0.2 % concentration of polymer and 0.1 % of sodium tripolyphosphate was superior over high and low concentration of polymer and sodium tripolyphosphate.


Fig. 11.  SEM photomicrograph of Lovastatin pure drug

(×6500). Scale bar  2 μm



Fig. 12.  SEM photomicrograph of Lovastatin Nanopaticles (CL4)

(×1,000).Scale bar =10 μm




Chitosan molecular weight, polymeric composition and polymer/drug ratio in the nanoparticles did not influence the particle size characteristics.  Because chitosan and the drug is oppositely charged, their electrostatic interaction may be advantageous for the formation of Chitosan nanoparticles that exhibit high encapsulation efficiencies. Thus, nanoparticles prepared by ionotropic gelation method using chitosan as polymer and sodium tripolyphosphate as crosslinking agent, produced particles of good stability. It seems that the relatively lower viscosity of chitosan with a concentration (0.1%) and an appropriate concentration of STPP (0.1 %w/v), and chitosan concentration (0.2 %) and concentration of STPP (0.1 %w/v) promoted the formation of nanoparticles at lower size. A fixed sonication time of 20 min yielded smaller and more uniform nanoparticles. Zeta potential of the developed formulation was in the range of 25 - 32 mV, which suggests that the formulation was fairly stable. The higher zeta potential indicate that chitosan nanoparticles were stable. It seems likely that the long amino groups hinder anion adsorption and keep high the value of the electrical double layer thickness, and thus preventing aggregation. Furthermore, the SEM image showed that each particle unit exhibited a nanostructure. The nanoparticles also exhibited sustained drug release behavior.



This paper report, the possibility to entrap hydrophobic lovastatin within CS-STPP nanoparticles using a modified ionotropic gelation technique, strong electrostatic interactions exist in the nanoparticles. Chitosan nanoparticles herald a novel controlled drug delivery, which offer several potential benefits. Chitosan nanoparticles had shown an excellent capacity for the association of lovastatin. The present study was aim to develop lovastatin loaded chitosan Nanoparticles. Chitosan concentrations and drug/ polymer ratio in the nanoparticles influence the physiochemical characteristics such as zeta potential, polydispersity index, and average nanosize diameter or percentage encapsulation efficiency of lovastatin. Average Nanosize diameter, Polydispersity index, zeta potential, percentage encapsulation efficiency, stability study was found to be good for optimum formulation (CL4, 0.1%). The concentration of polymer and crosslinking agent are the important factors in the development of lovastatin nanoparticles. In conclusion, this work was confirms that modified ionic gelation method is offers an interesting potential for the delivery of hydrophobic drugs with chitosan nanoparticles.



Authors are wish to acknowledge Aurobindo Pharmaceutical Ltd. (Hydrabad, India), for providing lovastatin as gift sample. We also grateful  to Bharati vidyapeeth, Poona college of Pharmacy, Pune and Govt. college of pharmacy, Aurangabad for providing Malvern Mastersizer facility, Shivaji university Kolhapur and University of pune, Pune  for SEM, DSC and XRD facilities. We also grateful to Sinhgad College of Pharmacy, vadgoan, pune for providing Freeze dryer facility.



1.        Muller, R.H., Bohm, B.H.L, Nanosuspensions, in Emulsions  Nanosuspensions  for  the formulation of poorly soluble drugs, Muller R.H., Bentia S., and Bohm B.H.L  Eds. 1998 (Medpharm Scientific Publishers), Stuttgart, Germany.

2.        Prasad, N., Pudavar, H.E., Baba, Koichi, Roy, I, Ohulchansky, T., et al. Method for delivering hydrophobic drugs via nanocrystals, 2007, United States Patent 0134340.

3.        Deleers, M., Hecq, J., Fanara, D., Vranckx, H., Amighi, K.,Preparation and  characterization of nanocrystals of nifedipine for solubility and dissolution rate enhancement. Int J Pharm., 2005; 299: 167-177.

4.        Couvreur, P., Vauthier, C., Nanotechnology: intelligent design to treat complex disease. Pharm Res., 2006; 23(7): 284-288.

5.        Mohanraj, V.J., Chen, Y., Nanoparticles - a Review., Trop J Pharm Res., 2006; 5(1): 561-573.

6.        Majeti, N.V., Kumar, R., Nano and microparticles as controlled drug delivery devices, J. Pharm Sci., 2000;3(2): 234-258.

7.        K. A. Varady, and P. J. H. Jones,“Combination diet and exercise interventions for the treatment of dyslipidemia: an effective preliminary strategy to lower cholesterol levels?” Journal of Nutrition, 2005;135(8): 1829–1835.

8.        Y., Luo, G., Chen, B., Li., et al.,“Dietary intervention with AHP, a functional formula diet, improves both serum and hepatic lipids profile in dyslipidemia mice,” Journal of Food Science, 2009; 74(6): 189–195.

9.        Nti-Gyabaah, J., Chmielowski, R., Chan, V., Chiw, Y.C., Solubility of lovastatin in a family of six alcohols: Ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol and 1- ioctanol. Int J Pharm. 2008, 359: 111-117.

10.     Gande, Suresh, Majunath, K., Venkateswarlu, Satyanarayana, V.,Preparation, Characterization, and in vitro, in vivo evaluation of lovastatin solid lipid nanoparticles.AAPS PharmSciTech 2007; 8: 24.

11.     Illum, L. Chitosan and its use as a pharmaceutical excipient. Pharm. Res. 1998; 15: 1326-1331.

12.     Janes, K. A., M. P. Fresneau, A. Marazuela, A. Fabra, and M. J. Alonso., Chitosan nanoparticles as delivery systems for doxorubicin. J. Control. Release, 2001; 73:  255-267.

13.     M., Sumiyoshi, and Y. Kimura, “Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice,” Journal of Pharmacy and Pharmacology, 2006; 58(2): 201–207.

14.     H. L. Zhang, S. H. Wu, Y., Tao, L. Q. Zang, and Z. Q. Su, “Preparation and characterization of water-soluble chitosan nanoparticles as protein delivery system,”  Journal of Nanomaterials, 2010; Article ID 898910, 5 pages,

15.     S. Hirano, H. Seino, I. Akiyama, and I. Nonaka,, Chitosan: a biocompatible  material for oral and intravenous administration. In C. G. Gebelein and R. L. Dunn (eds.), Progress in Biomedical Polymers, Plenum Press, New York, 1990; 283–289.

16.     N.G.M. Schipper, S., Olsson, J., Hoogstraate, A., de Boer, and K.M. Varum., Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm. Res., 1997; 14:923–929.

17.     Q., Li, T., Dunn, E.W. Grandmaison, M.,F.,A., Goodsen, Applications and properties of  chitosan, J. Bioact. Compatible Poly. 1992; ,7: 370–397.

18.     MI, FL, Shyu, S.S.Kuan, C.Y.Lee, S.T Lu, K.T. Jang, S.F., Chitosan polyelectrolyte complexation for the preparation of gel beads and controlled release of anti- cancer drug.Enzymatic hydrolysis of polymer. J. Appl. Polym. Sci., 1990; 74:1868-1879.

19.     Shu, X. Z. Zhu, K.J., A novel approach to prepare tripolyphosphate /chitosan complex beads for controlled drug delivery., Int. J. Pharm., 2000 201:51-58.

20.     Mi, FL, Shyu, S.S. Lee, S.T. Wong, T.B., Kinetic study of chitosan-tripolyphosphate complex and acid resistive properties for the chitosan-tripolyphosphate gel beads prepared by in-liquid curing method., J. Polym. Sci. Polym. Phys., 1999; 37:1551–1564.

21.     Calvo P., Remuñan-López C., Vila-Jato J.L., Alonso M.J., Pharmaceutical Research, 1997, 1431-1436.

22.     Lim, L.Y., Wan, L.S.C., Thai, P.Y. Chitosan microspheres prepared by emulsification and ionotropic gelation, Drug Dev. Ind. Pharm., 1997; 23: 981-985.

23.     Maitra, A., Banarje, T., Mitra, S., Sing, A.K. and Sharma, R.K.,Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int. J. Pharms., 2002; 243:93-105.

24.     Barratt G., Characterization of colloidal drug carrier systems with zeta potential measurements., Pharm. Technol. Eur., 1999; 11: 25-32.

25.     Shiraishi, S., Imai, T., Otagiri, M., Controlled release of indomethacin by chitosan-polyelectrolyte complex: optimization and in vivo/in vitro evaluation, J. Control. Release., 1993; 25: 217-225.






Received on 15.09.2011          Modified on 28.09.2011

Accepted on 05.10.2011         © RJPT All right reserved

Research J. Pharm. and Tech. 4(12): Dec. 2011; Page 1869-1876