Sarita Gaikwad, Preeti K Suresh

University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.)

 *Corresponding Author: suresh.preeti@gmail.com

Abstract

Background: Magnetically Responsive Mesalamine Microspheres is an effective strategy for localized drug delivery only at the target site for the treatment of Irritable Bowel Diseases and thereby minimizing the dose and drug induced toxicity.

Objective: The main objective of the study is to localize the drug only at the target site thereby minimizing the dose.

Result and Discussion: 1. The aim of present study was to formulate Magnetically Responsive Mesalamine Microspheres by solvent evaporation method using biodegradable polymers Chitosan and Pectin and carry out the various pharmaceutical and magnetic characterizations, to study the effect of polymer type on in-vitro drug release and preclinical in-vitro screening studies such as in- vitro release studies using microflora activated system and in-vitro anti-inflammatory activity. 2. Chemical compatibility study was performed using FTIR spectroscopy. FTIR spectroscopy studies indicated that the Mesalamine is compatible with polymers. The spectra showed no changes in the major peaks thus confirming no interactions between drug and polymers. 3. Calibration curves of Mesalamine was constructed in Phosphate Buffer Saline pH7. 4. Magnetite (Fe3O4) (used as magnetic carrier) was chemically synthesized using precipitation method.5. In the present study, 3 formulations were prepared in total by using Chitosan and Pectin as polymer in different ratios (1:1,1:2 and 1:3) of each polymer and combination of two polymers. Also, the effect of polymer type was studied.

Conclusion: It can be concluded that the Magnetically Responsive Mesalamine Microspheres offer a localized drug delivery only at the target site by the combined effect of physical approach (utilizing the principle of magnetic targeting with an intention to produce a depot near the target organ) and biochemical approach (using biodegradable polymers chitosan and pectin for drug release in a controlled manner). By producing a depot near the target organ, unwanted distribution of drug to non-target organ can be avoided.

Keywords: Inflammation, magnetically responsive microspheres, Mesalamine, IBD

 

Introduction

CTDDS means targeted delivery of drugs into the lower GIT, which occurs primarily in the large intestine (i.e., colon). In the past two decades, the pharmaceutical scientists have extensively investigated in the area of colonic region for targeted drug delivery.(Mukesh et al. 2013) Colon targeting depends on exploiting a unique feature of specific site and protecting the drug until it reaches to the site.

Fig. 1 Anatomy of colon

Targeted drug delivery to the colon is highly desirable for local treatment of a variety of bowel diseases such as inflammatory bowel disease, amebiasis, colonic cancer and for local treatment of local colonic pathologies, and the systemic delivery of protein and peptide drugs.(“Pharmaceutical Approaches to Colon Targeted Drug Delivery Systems.” n.d.) The advent of slow release technologies increases the chances for a drug to be released in the colon and thus this organ has an important role to play in drug absorption from oral sustained release formulations.

Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers having a particle size ranging from 1-1000µm.

Microspheres are defined as “monolithic spheres or therapeutic agent distributed throughout the matrix either as a molecular dispersion of particles” or can be defined as structure made up of one or more miscible polymers in which drug particles are dispersed at the molecular or macroscopic level.

There are two types of microspheres:

Ø  Microcapsules

Ø  Micro matrices

Microcapsules are those in which entrapped substance is distinctly surrounded by distinct capsule wall and micro matrices in which entrapped substance is dispersing throughout the microsphere’s matrix. They are made up of polymeric, waxy, or other protective materials, that is biodegradable synthetic polymers and modified natural products.

PATHOPHYSIOLOGY (Patra, Shukla, and Das 2020),(Ritter et al. 2008)

Multiple etiologies have been proposed for IBD, but the precise cause is unknown. When a luminal antigen crosses the epithelial layer, T- lymphocytes (helper cells and cytotoxic cells) are activated. These t-cells are normally found in gut wall but in IBD, the normal regulation of their activity is disturbed. Helper T-cells, type-1 (Th-1), are associated principally with CD, whereas Th-2 cells are associated principally with UC.

 

Fig. 2 Molecular structure of microsphere

In UC, with the influx of neutrophils in lamina propia, there is localized collection of pus cells surrounded by inflamed tissues and causes depletion of mucin. Activation of mucosal inflammatory cells also leads to the production of large number of inflammatory mediators such as cytokines, leukotrienes, prostaglandins, platelet activating factor, oxygen radicals, thromboxanes and proteases etc. which are atleast partly responsible for tissue damage.

In CD, the accompanying inflammation is described as irregular/ patchy, segmented, and transmural. Most commonly, terminal ileum exhibits early lesions on or near Peyer’s patches.(Patra, Shukla, and Das 2020)

Fig 3 - Pathophysiology of IBD

MATERIALS AND METHOD

Mesalamine and Chitosan, Sigma Aldrich, Pectin and Magnesium Stearate, HI Media Laboratories Pvt. Ltd, Mumbai, Talc, MMC Health care, Chennai, Liquid Paraffin and Sodium Hydroxide, Aventor performance materials, Thane,Maharashtra, Ferrous Sulphate, Finar chemicals, Ahmedabad, Tween 80 and Span 80, Supra Chemicals, Chennai. Potassium dihydrogen ortho Phosphate, Disodium hydrogen phosphate, Sodium chloride, Hydrochloric acid, Glacial acetic acid, Dist. Water, Glutaraldehyde, Toluene, n-Hexane, Span 80.

PREFORMULATION STUDIES

The preformulation studies are the first step in the rational development of any formulation. It can be defined as “investigation of physical and chemical properties of drug substance alone and combined with the excipients. “The overall objective of preformulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms that can be mass produced.

The goals of the study are:

Ø  To establish physical characteristics.

Ø  To establish its compatibility with the excipients.

Ø  To determine kinetic rate profile.

DRUG-POLYMER INCOMPATIBILITY STUDIES

Fourier Transform Infra-Red Spectroscopy

The compatibility between pure drug and polymer was detected by FT- IR spectra. 1-2mg of Mesalamine alone, mixture of drug and excipients were weighed and mixed properly with Potassium bromide uniformly. The spectra were recorded over the wave number 4000- 500cm^-

CALIBRATION CURVE FOR MESALAMINE

Preparation of Phosphate Buffer Saline (PBS) pH 7.4

2.38g of disodium hydrogen phosphate, 0.19g of potassium di-hydrogen phosphate and 8.0g of sodium chloride was dissolved in sufficient distilled water to produce 1000ml. Then the pH was adjusted, if necessary.

Preparation of 0.1N Hydrochloric acid (pH 1.2)

8.5ml of conc. HCl was dissolved in 1000ml of distilled water. Then the pH was adjusted, if necessary.

Standard Curve in Phosphate Buffer Saline pH 7.4

100 mg of Mesalamine was transferred into a volumetric flask and dissolved in 15ml of 0.1N hydrochloric acid and the volume was made up to 100ml with PBS pH 7.4. The resulting solution was labeled as stock solution 1. From this stock solution, 10ml was taken and diluted to 100ml with Phosphate buffer saline pH 7.4 was labeled as stock 2. From this stock solution, 4ml, 8ml, 12ml, 16ml, 20ml, 24ml and 28ml were pipetted out into separate standard flasks and made up to 100ml with Phosphate buffer saline pH 7.4. The absorbance of solution was measured at 230nm using UV- Visible Spectrophotometer. The calibration curve was then plotted taking concentration on X- axis and absorbance on Y- axis.

PREPARATION OF MESALAMINE MAGNETIC MICROSPHERES

Preparation of Magnetite

The magnetite (Fe₃O₄) was prepared by reacting 10%w/v ferrous sulphate (containing 5% tween 80) with 20%w/v sodium hydroxide solution, followed by washing of the precipitate with dilute ammonia in order to get magnetite free of sulphate ions. This precipitate of magnetite was then dried at 100⁰C and passed through sieve no.300.

 

Fig 4(a) - MAGNETIC BEHAVIOUR OF THE PREPARED MICROSPHERES

Fig 4(b) - AFTER 30 SEC MAGNETITE MOVE TOWARDS THE DIRECTION OF MAGNETIC FIELD

Preparation of Glutaraldehyde saturated toluene (GST)

Glutaraldehyde (100ml) and toluene (100ml) were placed in a beaker and stirred at 1000rpm for one hour using a magnetic stirrer. Then the solvent mixture was kept overnight for stabilization after which the upper toluene layer saturated with glutaraldehyde was decanted and used as glutaraldehyde saturated toluene (GST).

Preparation of Dummy Magnetic Microspheres

Dummy magnetic microspheres were prepared by O/O solvent evaporation with chemical cross-linking method. Accurately weighed quantity of polymer was dissolved in 10ml of 1% glacial acetic acid. 10mg of   magnesium stearate was then added to the polymer-drug solution. Finally, specified amount of magnetite was added to this solution. The organic phase was drop-wise to 30ml of liquid paraffin containing 2% Span 80 and stirred at a speed of 1500rpm at 800C using high speed homogenizer. Stirring was continued for 1 h after the complete addition of polymer solution into oil. After 1 h stirring, 1-2 ml of GST was added dropwise added to the mixture with continuous stirring at 500 rpm for the next 1 h at a temperature 50-550 C. stirring was stopped after 1 h of addition of GST. Suspension of microspheres in paraffin oil thus obtained was centrifuged and the clear supernatant was decanted. Microspheres were then filtered and washed 3 times with hexane to remove liquid paraffin and then with distilled water to remove unentrapped drug from the surface of the microsphere. After that the microspheres were air dried and stored in dessicator at room temperature.

Table 1: Formulation of Dummy Magnetic Microspheres

Form ulatio n code	Polymer (mg)		Magn etite (mg)	Magnesiu m Stearate 5% (mg)	Liq. paraffin (ml)	Span 80 (ml)	Drug: Polymer ratio
	Chitosan	Pectin
F1	125	-	50	10	30	0.6	1:1
F2	-	125	50	10	30	0.6	1:1
F3	62.5	62.5	50	10	30	0.6	1:1

 

Preparation of Mesalamine Magnetic Microspheres

A Magnetic Microsphere of Dummy was prepared by O/O solvent evaporation with chemical crosslinking method. Accurately weighed quantity of polymer was dissolved in 10ml of 1% glacial acetic acid and accurately weighed drug was dissolved in minimum quantity of 0.1N HCl and added into the polymer solution. 10mg of   magnesium stearate was then added to the polymer-drug solution. Finally, specified amount of magnetite was added to this solution. The organic phase was drop-wise to 30ml of liquid paraffin containing 2% Span 80 and stirred at a speed of 1500rpm at 80⁰C using high speed homogenizer. Stirring was continued for 1 h after the complete addition of polymer-drug solution into oil. After 1 h stirring, 1-2 ml of GST was added dropwise to the mixture with continuous stirring at 500 rpm for the next 1 h at a temperature 50-55⁰ C. Stirring was stopped after 1 h of addition of GST. Suspension of microspheres in paraffin oil thus obtained was centrifuged and the clear supernatant was decanted. Microspheres were then filtered and washed 3 times with hexane to remove liquid paraffin and then with distilled water to remove unentrapped drug from the surface of the microsphere. After that the microspheres were air dried and stored in dessicator at room temperature.

Table 2: Formulation of Mesalamine Magnetic Microspheres

Formulation code	Drug (mg)	Polymer 0(mg)		Magn etite (mg)	Magnesium Stearate 5%(mg)	Liq. paraffin (ml)	Span 80 (ml)	Drug: Polymer ratio
		Chitosan	Pectin
F1	125	125	-	50	10	30	0.6	1:1
F2	125	-	125	50	10	30	0.6	1:1
F3	125	62.5	62.5	50	10	30	0.6	1:1

Fig 5 - FORMULATED MESALAMINE MAGNETIC  MICROSPHERES

EVALUATION OF MAGNETIC MICROSPHERES

PHYSICOCHEMICAL CHARACTERIZATION

Shape and surface morphology studies using Optical Microscope

The shape and surface morphology of magnetic microspheres were investigated using optical microscopy. The samples for EM study were prepared by lightly sprinkling the formulation on a slide and then covered with a cover slip and the prepared slide was then observed under the optical microscope.

Particle Size Analysis

The Mesalamine Magnetic Microsphere were analyzed for their size and polydispersity index on Zetasizer Nano ZS, Malvern instruments, based on photon correlation spectroscopy, at a scattering angle of 90° and temperature of 25°. Measurements were carried out both for fresh and air-dried samples. Before counting, the samples were diluted with a phosphate buffer at pH 7.4 and 0.1N HCl and were sonicated in order to prevent precipitation during the measurements.

Surface charge (Zeta-potential)

The surface charge of the mesalamine magnetic microspheres was determined with Zetasizer Nano ZS, Malvern instruments. The measurements were carried out in an aqueous solution of KCl 0.1N solution. The measured values were corrected to a standard reference for temperature of 20°.

Drug- Excipient Interaction

The FT-IR spectrum was recorded on Shimadzu FT-IR spectrophotometer, for the prepared mesalamine magnetic microspheres. The samples were prepared by grinding samples (5mg) with KBr (100mg) and then pressing the mixtures into pellets, further placed on a crystal sample holder and scanned from 4000cm^-1 to 400cm^-1.

Melting point

Melting point of drug sample was performed to determine the purity of the sample. The impurity present in small amount was detected using capillary method in Melting Point Apparatus, Electronics India and model no. 931.

Partition coefficient

Partition coefficient was performed by taking 10mg of drug dissolved in 10ml of octanol and 10 ml of distilled water and kept for 24 hrs. After then, the separated distilled water was analyzed spectrophotometrically in UV spectroscopy at 230 nm.

Solubility studies

Solubility profile of drug determined using different solvents such as distilled water, phosphate buffer at different pH 4.5, 6.0, 7.2, 7.5 and 0.1N HCl. A saturated solution was prepared by adding 10mg drug in 10ml of solution and then analyzed using UV spectrophotometer at 230 nm.

PHARMACEUTICAL CHARACTERIZATION

Percentage Yield

Microspheres were weighed and the percentage yield was calculated by taking into consideration the total weight of the drug and excipients used for preparation of microspheres.

Percentage Yield =	Practical yield	X 100
	Theoretical yield

 Estimation of Drug Content and Entrapment Efficiency

50mg of microspheres was weighed and dissolved in 2.5ml of 0.1N HCl and suitably diluted with phosphate buffer saline pH 7.4 in 50 ml standard flasks. The solution was kept for 24hrs and filtered to separate the fragments. Drug content was analyzed after suitable dilution by UV spectrophotometer at a wavelength of 230 nm against phosphate buffer saline pH 7.4 as blank. The drug content of each formulation was calculated using the following equation

Percentage Drug Entrapment Efficiency =	Actual Drug Content	X 100
	Theoretical Drug Content

 

 

 Drug Loading Capacity

Drug loaded microspheres were mixed in 2.5ml of 0.1N HCl and suitably diluted with phosphate buffer pH 7.4 at room temperature and kept for 24 h. After filtration and suitable dilution, Mesalamine present in the solution was determined.

% Drug Loading =	Quantity of the drug present in the microspheres	X 100
	Weighed quantity of microspheres

 

in- vitro Drug Release Study

The in- vitro drug release study was carried out in paddle apparatus using a mixture of 45ml of 0.1N HCl   and 855ml of   PBS pH 7.4 as the dissolution medium maintained at 37⁰C+ 0.5⁰C. Weighed microspheres containing 50mg of drug were introduced into the dissolution medium. Aliquots were taken at regular time intervals and after suitable dilution, percentage drug release analysed by UV Spectrophotometer at 230nm.

RELEASE KINETICS OF THE OPTIMIZED FORMULATION

The in- vitro release data for the optimized batch was fitted to various release kinetic models (Zero-order, First- order, Higuchi, Hixon- Crowell and Korsmeyer- Peppas models). The goodness of fit was found out to describe the kinetics of drug release.

Zero order release model

Zero order models describe the systems where the drug release rate is independent of its concentration of the dissolved substance.

C = Ko t

Where, C- Cumulative percentage drug released Ko – zero-order constant

t- time

A plot of time on x- axis and cumulative percentage drug released on y-axis gives a straight line with slope, Ko if it follows zero-order Kinetics.

Application: This relationship can be used to describe the drug release of several types of modified release pharmaceutical dosage forms like transdermal systems, matrix tablets with low soluble drugs in coated forms and osmotic systems.

First order release model

First order models describe the systems where the release rate is dependent on the concentration of the dissolved substance.

Log C = log Co – K t / 2.303

Where, C – Cumulative percentage drug remaining C_o- Initial concentration of drug

K – First order constant

 

A plot of time on x-axis and log cumulative percentage drug remaining on y – axis gives a straight line with slope, K / 2.303 if it follows first- order kinetics.

Application: This relationship can be used to describe the drug dissolution in pharmaceutical dosage forms containing water –soluble drugs in porous matrices.

Higuchi release model

The Higuchi model describes the release from systems where the solid drug is dispersed in an insoluble matrix and the rate of release is related to the rate of drug diffusion.

Q = K √t

Where, Q – Cumulative percentage drug released

K- Constant reflecting the design variables of the system t – Time

 

A plot of square root of time on x-axis and cumulative percentage drug released on y- axis gives a straight line if it follows Higuchi Kinetics.

Application: This relationship can be used to describe the drug dissolution from several types of modified release pharmaceutical dosage forms like some trans-dermal systems and matrix tablets with water soluble drugs.

Hixson-Crowell release model

The Hixson-Crowell cube root model describes the release from systems where there is a change in surface area and diameter of the tablets or particles.

Q ^1/3 – Qt^1/3 = K         K t

Where, Qt – Cumulative percentage drug released in time t Q_o – initial amount of the drug

K_HC – the rate constant for Hixson-Crowell rate equation K – Constant incorporating the surface volume relation

A plot of time on x-axis and cube root of cumulative percentage of drug remaining on y-axis gives a straight line if it follows Hixson-Crowell kinetics.

Application: This equation applies to dosage forms like tablets, where the dissolution occurs in planes that are parallel to the drug surface if the tablet dimensions diminish proportionally, in such a manner that the initial geometrical form keeps constant.

Kors Meyer and Peppa’s Model:

Kors Meyer and Peppa’s Model derive a simple relationship which describes the drug release from a polymeric system.

M_t / M_α = K t ⁿ

Where, M_t / M_α – fraction of drug released at time t K - Release rate constant

n - Release exponent

A plot of log time on x-axis and log cumulative percentage of drug released on y-axis gives a straight line, if it follows Korsmeyer and Peppas kinetics.

DIFFUSION COEFFICIENT	OVERALL SOLUTE RELEASE MECHANISM	EFFECT ON DRUG11 RELEASE
0.45	Fickian diffusion	Only due to diffusion through the matrix
0.45<n<0.89	Anomalous (non-fickian diffusion)	Drug diffusion and polymer relaxation (erosion)
0.89	Case-II transport	Only due to polymer relaxation (erosion)
n>0.89	Super case-II transports

 

 

In-vitro drug release data were fitted to various models such as zero-order, first- order, Higuchi equation, Kors Meyer- Peppa’s equation, and Hixson-Crowell equation to know about the mechanism of drug release:

1.     C versus t (zero order)

2.     log C versus t (first order)

3.     Q versus square root of t (Higuchi)

4.     Q_t versus cube root of t (Hixson-Crowell)

5.     log% Q_t versus log t (Kors Meyer- Peppa’s)

P-XRD Analysis:

Powder XRD of formulation mixture of mesalamine with chitosan and pectin was recorded using PANlytical X ray diffractometer with Si (Li) PSD detector. The operation data were measuring circle diameter – 435, 500 and 600 mm predetermined; angle range-120°, X-ray source- Cu, wavelength 1.5406

Differential Scanning Calorimetry

The DSC analysis of pure drug was carried out using differential scanning calorimeter (METLER TOLEDO). Sample of about 5mg was placed in a 50 µl perforated aluminium pan and sealed. Heat runs for each sample were set from 5°C to 300°C using nitrogen as purging gas and sample.

RESULTS AND DISCUSSION

PREFORMULATION STUDIES

Drug- Polymer Compatibility Studies using FTIR Spectroscopy

The compatibility between drug and polymer was confirmed by using FTIR spectroscopy.

Infrared spectroscopic       analysis            for           drug (Mesalamine),                                           Polymers (Chitosan, Pectin), magnesium stearate and Drug-Polymer mixture were carried out.

The principal IR peaks of pure Mesalamine and polymers Chitosan and Pectin in   figure 6-11.

Fig 6 - FTIR spectra of (Mesalamine + Chitosan) Vs. Mesalamine

 

Interpretation:

 From the Fig.6 it could be interpreted 2800-2900 shows O-H stretching of carboxylic acid, 3000-3050 shows Ar-H stretching, 1550-1600 shows C=C stretching, 3600-3700 shows phenolic O-H stretching, 1680-1700 shows C=O stretching of carboxylic acid, 3300-3450 shows N-H stretch. The FTIR study revealed that there is no interaction between the drug and polymer, since the major peaks of the drugs are not affected by the excipients.

Fig 7 - FTIR spectra of (Mesalamine + Pectin) Vs. Mesalamine

In Fig.7 2800-2950 shows O-H stretching of carboxylic acid, 3000-3050 shows Ar-H stretching, 1550-1600 shows C=C stretching, 3600-3700 shows phenolic O-H stretching, 1680-1700 shows C=O stretching of carboxylic acid, 3200-3400 shows N-H stretching. The FTIR study revealed that there is no interaction between the drug and polymer, since the major peaks of the drugs are not affected by the excipients.

Fig 8 - FTIR spectra of (Mesalamine + Pectin) Vs. Mesalamine

In Fig. 8 72800-2950 shows O-H stretching of carboxylic acid, 3000-3050 shows Ar-H stretching, 1550-1600 shows C=C stretching, 3600-3700 shows phenolic O-H stretching, 1680-1700 shows C=O stretching of carboxylic acid, 3200-3400 shows N-H stretching. The FTIR study revealed that there is no interaction between the drug and polymer, since the major peaks of the drugs are not affected by the excipients.

  Fig 23 - First Order Kinetics for Optimized Formulation F3

 

Fig 24 - Korsmeyer Peppas Release Kinetics for Optimized Formulation F3

 

Fig 25 - Hixon Crowell Kinetics for Optimized Formulation F3

 

Fig 26- Higuchi Diffusion Kinetics for Optimized Formulation F3

The coefficient of determination (R2) was taken as criteria for choosing the most appropriate model. The R2 values of various kinetic models are in table 26.

Table 10: R² values of various kinetic models

Kinetic model	Coefficient of determination (R2)
Zero order	0.956
First order	0.745
Korsmeyer and Peppas	0.975
Hixson-Crowell	0.864
Higuchi	0.797

 

Ø  The order of drug release was found to be Zero order, in which regression value was 0.956.

Ø  The ‘n’ value of Korsmeyer peppas equation was found to be 1.372. From this it was concluded that the drug release follows a Super-Case II transport in which the drug release mechanism may be due to polymer relaxation (erosion) alone.(D. Chandra et al.),(Raj et al. 2013)

 

 Differential Scanning Calorimetry

Pure     mesalamine   has an endothermic melting peak at 286˚C   representing its crystalline nature. Moreover, chitosan and pectin have a sharp endothermic peak at 320˚C which is related to its crystalline matter and also the amount of water loss which is linked    to the hydrophilic groups of the polymer. The calorimetry of magnetic microspheres demonstrated mesalamine peak shifted from 286 to 283 ˚C, showing a reduction in its glass-transition temperature. When the crystal part of network increases, the amorphous part i.e., related to Tg decreases and the terminal zero shear viscosities of the systems were always found to decrease upon microspheres addition, paralleling the reduction of the Tg.

X RAY DIFFRACTION

XRD patterns showed a sharp intense peak at 15.167° indicating that

the drug and the polymer existed in the crystalline state.

CONCLUSION:

The aim of the present study was to formulate magnetically responsive mesalamine microspheres by solvent evaporation method by using biodegradable polymers (Chitosan and Pectin) and to carry out the various pharmaceutical and magnetic characterizations, to study the effect of polymer type on in-vitro drug release. In the present study, 3 formulations were prepared in total by using Chitosan and Pectin as polymer in different ratios (1:1) of each polymer and combination of two polymers. Also, the effect of polymer type was studied. Among the different formulations, F3 gave satisfactory results by releasing 100.64 % in 9 hours. The results indicate that the chitosan-pectin microspheres substantially retarded the drug release and showed the best result for the one with higher chitosan content (i.e., F3 formulation). The inter polymer complex that could be formed between carboxyl groups of pectin and the amino groups of chitosan, may be responsible for such delayed drug release. The in-vitro release study of optimized formulation F3 was applied to various kinetic models to predict the mechanism of drug release. The drug release was found to follow zero order kinetics. In Korsemeyer Peppas equation, the n value was 1.372, indicating anomalous diffusion or non-fickian diffusion, probably Super-Case II transport in which the drug release mechanism may be due to polymer relaxation(erosion) alone.

FUTURE SCOPE

Ø  In- vitro screening using cell culture models

Ø  In- vivo screening using animal models (using gamma scintillography).

Ø  Pharmacokinetic and toxicity study

Ø  Combinational therapies showing synergistic effect can also need to be studied.

The adoption of magnetic particles for targeted delivery is minimal and most of the work is in the basic research phase. Hence their potential is yet to be realized fully. The future holds great promise for its systematic investigation and exploitation.