Evaluation the Surface Modification of Magnetic

Nanoporous Adsorbent in Drug Delivery System

By
ALI MOHAMMED HAMZA NASER
Supervised
By
Assist. Prof. Dr. Talib M. Albayati
 Drug Delivery
A drug delivery system (DDS) is defined as a formulation or a device that enables
the introduction of a therapeutic substance in the body and improves its efficacy
and safety by controlling the rate, time, and place of release of drugs in the body.

The ideal drug delivery system ought to be:

1. Biocompatible.
2. Automatically sturdy.
3. Comfy for the patient.
4. Proficient of attaining high drug loading,
5. Safe from accidental release.
6. Protection of the drugs from decomposition.
7. Zero premature release.
 Controlled Drug Delivery

The potential advantages of controlled drug delivery which are:

(1) Avoiding patient compliance.
(2) Prolonging delivery.
(3) Reduced the side effects of the drug.
(4) Economic causes
(5) the treatment efficiency can be promoted via controlling the conditions.
Nano porous materials have been classified by IUPAC into three types
which are:

1 2 3

microporous, macroporous
mesoporous,
have pore have pore
have pores in
size smaller size larger
the size
than 2 nm than 50 nm
range of 2
and 50 nm
Mesoporous Silica
Mesoporous silica nanoparticles (MSN) have been broadly applied in the areas of catalysis,
adsorption and separation processes. More recently, these ordered mesoporous materials have been
used also as matrices as storage vehicles in controlled drug delivery systems owing to their large
surface areas, tunable pore sizes, good biocompatibility and facile surface functionalization. The
making of these materials interesting as drug delivery carrier due to its good properties such as
zero premature release, high loading capacity of the drug, tailored drug release, high
bioavailability, enhanced the rate of dissolution and targeting the desired cells.

Types of Mesoporous Materials

SBA family:-
Stucky and coworkers in 1998 have discovered a new type of highly ordered mesoporous
material which has a large pore diameter and large pore volume. Various kinds of SBA
families are SBA-1, SBA-3, SBA-15, and SBA-16.

A two – dimensional
channel

Hexagonal and amorphous type of

silica
SBA-15
High hydrothermal stability

Large pore size and pore volume

High surface area.

Non-cytotoxic
 • Iron oxide-based magnetic
nanomaterial is determined to
be one of the most well
Modification of established nano-materials in
the biomedical field
Mesoporous Silica considering their benign
The rapid development of biocompatibility, controllable
nanotechnology offers size, high stability, and the
opportunities for designing
potential applications
and manipulating novel
multifunctional nano-
materials.
 Have unique magnetic features not
present in other materials

Magnetic
Higher bioavailability
SBA-15

Increasing efficiency of
mesoporous silica

Magnetic Resonance Imaging (MRI)

 Nystatin
Nystatin (C47H75NO17) (NYS) is commonly employed to treat fungal infections in HIV-
infected. It’s used orally, but a disadvantage of these formulations is the limited residence
time of it's in the affected areas . The dosage form needs to reside at the site of infection for a
prolonged period. In addition, convenience of dosing is also an important factor. various
dosage forms available in the market are solutions, suppositories, creams, ointments, gels,
foams, sprays, tablets, capsules, etc. These conventional dosage forms tend to be leaky and
messy and are associated with poor retention, leading to poor patient compliance and loss of
therapeutic efficacy. These limitations can be overcomed by a drug delivery system because
of portability, convenient application, long retention time, easy storage and handling and
improved stability
 Meloxicam

Meloxicam (MLE) (C14H13N3O4S2 ) is a potent non-steroidal anti-

inflammatory drug , used orally to alleviate the symptoms of
osteoarthritis, rheumatoid arthritis, antipyretic properties, MEL inhibits
the growth of colorectal cancer cell, and leads to a decrease of the
synthesis of prostaglandins, therefore inflammation is reduced.
Objective of This research
1 Synthesis of mesoporous material SBA-15.

Modification the surface of SBA-15 by magnetic (Fe/SBA-15) with different loading ratio
2 (0.5%,1%,2%,3%) of pour volume of mesoporous(SBA-15)

Characterizations of (SBA-15 & Fe/SBA-15) by means of FT-IR, TGA, XRD, SEM and BET
3 surface area.

Nystatin and Meloxicam pharmaceutical compound will be loaded into the pores and surface
4 of mesoporous silica as drug delivery system by adsorption process from solution

5 Study the time of release(desorption) of the pharmaceutical compounds from the surface
mesoporous (SBA-15 and Fe/SBA-15)

Study the kinetic of drug release by using different kinetics model.

6

7 Validation and optimization the data of drugs loading by using Statistical Experimental Design.
Synthesis of SBA-15
Modification of SBA-15
 X-Ray Diffraction (XRD)
Scanning Electron Microscopy (SEM)
The Brunauer-Emmett-Teller Surface Area (SBET)
Thermal gravimetric analysis (TGA)
Fourier Transformed Infrared Spectra (FTIR)
 In drug loading
experiments,
different
parameters that
affect on the
loading processes
were studied as
can be shown in
the table below:
 Different conditions used for loading
Studied Variable (NYS by SBA-15) Range Units

Effect of pH 2 – 10 ‫ــــــــ‬

Effect of SBA-15 dosages 0.2 -0.02 g

Effect of NYS
80 -20 mg/l
Concentrations
Effect of Contact Time 48 -0.5 h

Units
Studied Variable (MEL by SBA-15) Range

Effect of pH 2 - 10 ‫ـــــــــــ‬
Effect of SBA-15 dosages 0.01 - 0.1 g
Effect of MEL
10 - 50 mg/l
Concentrations
Effect of Contact Time 4 - 72 h

Studied Variable (MEL by Fe/SBA-15) Range Units

Effect of pH 2 - 10 ‫ـــــــــ‬
Effect of SBA-15 dosages 0.01 - 0.1 g
Effect of MEL
10 - 50 mg/l
Concentrations
Effect of Contact Time 4 - 72 h
 Drug Release
The release of drugs
have done in
laboratory equipment
at given time intervals.
The suspension was
withdrawn by syringe
into a quartz cuvette.
The UV–Vis
spectrophotometer was
used to measure the
amount of the released
drugs NYS and MEL
at 305 nm and 362 nm
respectively
 Drugs Release (desorption)
Variables and conditions used for release drugs

Variables NYS/SBA-15 MEL/SBA-15 MEL/Fe-SBA/15

Media SBF (pH 7.4) SBF (pH 7.4) SBF (pH 7.4)

Mesoporous 0.14g SBA-15 0.03g SBA-15 0.04g Fe/SBA-15

Temperature 37 oC 37 oC 37 oC

Stirring 50 rpm 50 rpm 50 rpm

Time interval 0-72 hr 0-72 hr 0-72 hr

RESULTS
XRD For SBA-15 and Fe/SBA-15

XRD pattern of SBA-15andFe/ SBA-15

The Structure properties of SBA-15 and Fe/SBA-15

Si O2
d 100 a0 SBET Vp Dp Wt
Material Wt% Wt%
(nm) (nm) (m2/g) (cm3/g) (nm) (nm)
(EDX) (EDX)

SBA-15 10.3 11.89 772.52 1.07 5.29 6.6 48.5 51.5

Fe/SBA-
9.7 11.2 572.89 0.91 5.1 6.1 45.7 54.3
15
Scanning Electrons Microscope (SEM)

SBA-15

Fe/SBA-15
FTIR Spectra for SBA-15 &Fe/SBA-15
Thermal Gravimetric Analyses (TGA)
 Nystatin loading (Adsorption)
1. Effect of pH 2. Effect of SBA-15 Dose

3. Effect of Initial NYS Concentration 4. Effect of Contact Time

 The Best Parameter Conditions

Dose of Concentratio Contact

Factor pH DL%
SBA-15 n of drug time

NYS@SBA-
2 0.14gm 30mg/l 24h 90.47
15
Nystatin Release (desorption)
 Adsorption Isotherms Test

(a) Langmuir, (b) Freundlich and (c) Temkin isotherms.

Isotherm parameters for NYS loading with the correlation coefficient.

Langmuir Freundlich Temkin

Materials

bT
qmax KL Kf KT
RL R2 N R2 kJ/m R2
mg/g l/mg mg/g l/mg
ol

NYS@SBA-
14.92 0.056 0.37 0.751 3.385 0.986 0.967 0.593 16.76 0.923
15
 kinetic Release (desorption) of Nystatin

(a) First order Model, (b) Higuchi Model, (c) Korsmeyer_Peppas Model and (d) Weibull Model
 Release kinetic parameters of Nystatin from SBA-15

First order Higuchi Korsmeyer-peppos Weibull

drugs

K1 KH K (h-
R2 R2 R2 n R2 m
(h-1) (%h1/2) n)

NYS@SBA-15 0.993 0.0494 0.983 21.87 0.978 0.6089 17.9 0.995 0.7967
 Statistical Experimental Design for Nystatin Drug Loading
Model of NYS drug
linear Quadratic
Drugs
R2 Adj-R2 Pred-R2 R2 Adj-R2 Pred-R2

NYS@SBA-15 0.8693 0.8492 0.7642 0.9594 0.9446 0.2590

Mathematical Model
𝐃𝐋% 𝐍𝐘𝐒@𝐒𝐁𝐀 − 𝟏𝟓
= 5.90 − 3.62 ∗ pH + 1.64 ∗ Dose − 0.95 ∗ Conce. +0.74 ∗ Time − 0.33
∗ pH 2 − 1.65 ∗ Dose 2 − 1.65 ∗ Conce. 2 − 1.01 ∗ Time 2

The significant parameters of NYS loading

Source Mean Square F Value p-valu ' Prob > F''

A-pH 54.04 285.50 < 0.0001 significant

B-DOSE. 12.16 64.27 < 0.0001 significant

C-CONCE 3.52 18.59 0.0003 significant

D-Time 1.91 10.09 0.0044 significant

The Normal Plot of Experimental Values of Drugs
Loading
Response Surface Analysis for NYS drug
 Meloxicam Loading (Adsorption)

Effect of pH
Effect of SBA-15 and Fe/SBA-15 Dose
Effect of Initial MEL Concentration
Effect of Contact Time
Selecting of Operating Conditions for MEL Loading

Factor MEL@SBA-15 MEL@Fe/SBA-15

Constant room Constant room
Temperature
temperature temperature
pH 8 8

Dosage 0.03 0.04

Concentration 30 mg/l 40 mg/l

Time 24hr 24hr

Drug loading
31.81% 42.85%
efficiency %
Release (desorption)of Meloxicam
 Adsorption Isotherms Test

(a) Langmuir, (b) Freundlich and (c) Temkin isotherms for MEL@SBA-15 and Fe/ SBA-15
 Isotherm parameters for MEL loading with the correlation coefficient.

Langmuir Freundlich Temkin

Materials
bT
qmax KL Kf KT kJ/mo
(L/mg RL R2 N R2 R2
(mg/g) (mg/g) l/mg
) l

MEL@SBA-15 16.05 0.031 0.51 0.9691 0.144 0.647 0.9942 0.6 15.88 0.9591

MEL@Fe/SBA-15 16.77 0.028 0.64 0.9349 0.079 0.582 0.9915 0.6 15.88 0.9349
kinetic Release of MEL (desorption)
Release kinetic parameters of Meloxicam from SBA-15 & Fe/SBA-15

First order Higuchi Korsmeyer-peppos Weibull

Drugs

K1 KH K (h-
R2 R2 R2 n R2 m
(h-1) (%h1/2) n)

MEL@SBA-15 0.9845 0.0466 0.9772 21.598 0.9432 0.6549 16.6 0.9788 0.8376

MEL@Fe/SBA-15 0.9874 0.0257 0.9796 15.203 0.9494 0.7235 9.28 0.9538 0.3908
 Statistical Experimental Design for Meloxicam Drug Loading
Model of MEL drug
linear Quadratic
Drugs
R2 Adj-R2 Pred-R2 R2 Adj-R2 Pred-R2

MEL@SBA-15 0.7502 0.6977 0.5082 0.9205 0.8781 0.6861

MEL@Fe/SBA-15 0.7273 0.6699 0.5240 0.9226 0.8813 0.4045

Mathematical Model
DL% MEL@SBA − 15
= 5.74 + 2.16 ∗ pH + 0.24 ∗ Dose + 0.55 ∗ Conce. +0.67 ∗ Time − 1.85 ∗ pH 2
− 0.72 ∗ Dose 2 − 0.62 ∗ Conce2 − 0.70 ∗ Time 2
DL% MEL@Fe SBA − 15
= 42.77 + 14.62 ∗ pH + 7.29 ∗ Dose + 16.90 ∗ Conce. +9.28 ∗ Time − 3.89 ∗ pH 2
− 11.07 ∗ Dose 2 − 14.42 ∗ Conce. 2 − 15.77 ∗ Time2
The significant parameters of MEL loading
Mean F p-value
Square Value Prob > F
Source
SBA-15 Fe/SBA15 SBA-15 Fe/SBA15 SBA-15 Fe/SBA15

A-pH 14.08 8.66 100.60 50.27 < 0.0001 < 0.0001

B-DOSE. 0.22 2.45 1.59 14.21 0.2260 0.0019
C-CONCE 0.97 9.19 6. 91 53.37 0.0190 < 0.0001
D-Time 1.39 2.16 9.92 12.55 0.0066 0.0030
The Normal Plot of Experimental Values of Drugs Loading
The Predicted Vs. Actual & Residuals Vs. Actual Plots for MEL loading
(a & c) MEL@SBA-15 (b & d) MEL@Fe/SBA-15.
 Response Surface Analysis for MEL Drug
MEL@SBA-15
MEL @Fe/SBA-15
Conclusions
 Maximum drug loading efficiency for NYS by SBA-15 (90.47%) were
achieved in a loading system at pH(2), dosage of (0.14g), concentration
(30 mg/l) and contact time (24 h), and for MEL drug for SBA-15 and
1 Fe/SBA-15 (31.81% and 42.85%) respectively, at best condition pH(8),
dosage of (0.03, 0.04) gm, concentration (20, 30) mg/L and contact time
( 24) h for both SBA-15 and Fe/SBA-15 respectively.

The adsorption isotherms for NYS on to SBA-15 and for

MEL on to SBA-15 & Fe/SBA-15 have confirmed that the
2
loading processes can be well fit by the Freundlich isotherm
model as the best fit with a higher correlation coefficient
(0.9678, 0.9629 and 0.9724) respectively.

The release of NYS drug from SBA-15 could reach up 87.97% after 18h
3 and the release of MEL drug from SBA-15&Fe/SBA-15 could reach up
to 85.76% , 78.13% after 18h, 24 h respectively. The release of drugs was
examined in SBF media of pH 7.4.
For Future study
1. Study the effect of temperature on
drug loading.
2. Using another methods to increase the
solubility of drugs such us use the ionic
liquids methods or using the green
solvent.
3. Using another kinds of mesoporous
materials like MCM-41 as a carrier for
Meloxicam drug.