This study evaluates the applicability of the ordered mesoporous silicate SBA-15 as an excipient to enhance dissolution. 10 poorly insoluble drugs where taken (carbamazepine, cinnarizine, danazol, diazepam, fenofibrate, griseofulvin, indomethacin, ketoconazole, nifedipine, and phenylbutazone). SBA15 Synthesis was done by generic solvent impregnation method. Target drug content was 20 %.The drug content was checked by Thermogravimetric analysis. Nitrogen Physisorption method was used to calculate surface area of SBA 15. Physical properties where checked by DSC and Pharmaceutical performance and drug solubility was evaluated by In vitro dissolution. It was observed that the drug solubility of poorly soluble drugs where enhanced. The Aliquotes where stored for 6 months. Later again the Physical property and Pharmaceutical performance tests where performed by DSC and In vitro evaluation. It was found that the physical property and enhanced drug solubility was retained.

1. ORDERED MESOPOROUS SILICA MATERIAL SBA-15:
A BROAD-SPECTRUM FORMULATION PLATFORM FOR
POORLY SOLUBLE DRUGS
Presented By- Ojas Sawalikar Guide- Dr. M.H. Bele Co-Guide- Mrs. M.S. Sonawane
MVP Samaj’s college of Pharmacy, Nashik
M. Pharm. (1st year)
(Pharmaceutical Quality
Assurance Techniques)
M. Pharm. Ph.D.
(Pharmaceutics)
M. Pharm.
( Pharmaceutical Chemistry)
1

2. CONTENT
• Abstract
• Introduction
• Materials and Methods
- Model Drugs
- SBA-15 Synthesis
- Nitrogen Physisorption and Calculations
- Drug Loading
- Determination of Drug Loading
- Thermogravimetric (TG) Analysis
- Differential Scanning Calorimetry (DSC)
- In Vitro Dissolution
• Results and Discussion
• Conclusion
2

3. ABSRACT
This study evaluates the applicability of the ordered mesoporous silicate SBA-15 as an excipient
to enhance dissolution.
10 poorly insoluble drugs where taken (carbamazepine, cinnarizine, danazol, diazepam,
fenofibrate, griseofulvin, indomethacin, ketoconazole, nifedipine, and phenylbutazone).
SBA15 Synthesis was done by generic solvent impregnation method. Target drug content was 20
%.The drug content was checked by Thermogravimetric analysis.
Nitrogen Physisorption method was used to calculate surface area of SBA 15. Physical
properties where checked by DSC and Pharmaceutical performance and drug solubility was
evaluated by In vitro dissolution. It was observed that the drug solubility of poorly soluble drugs
where enhanced.
The Aliquotes where stored for 6 months. Later again the Physical property and Pharmaceutical
performance tests where performed by DSC and In vitro evaluation. It was found that the physical
property and enhanced drug solubility was retained.
3

4. INTRODUCTION
• The term mesoporous designates porous materials that possess pores with diameters
between 2 and 50 nm.
• For pharmaceutical use pore diameters that can be tuned between 2 and 30 nm, high
specific surface areas (up to 1500 m2/g) creating a high potential for adsorption,
large pore volumes (up to 1.5 cm3/g), and a silanol containing surface that can be
functionalized to modify drug release. SBA-15 can readily be prepared over a wide
range of uniform pore sizes, going from 5 to 30 nm.
• For pharmaceutical applications, the pore diameter usually varies between 6 and 10
nm. Typical values for the pore volume and surface area range from 0.8 to 1.2 cm3/g
and 600 to 1000 m2/g, respectively.
• The pore network of SBA-15 consists of a hexagonally ordered array of uniform two-
dimensional mesopores, with a complementary system of disordered
micropores(diameter<2 nm) that are located in the mesopore wall. The large internal
pore volume of SBA-15, combined with its highly accessible pore network, enables
drug loadings that can increase up to 50% (w/w). Because of its high drug loading
capacity, its relatively wide pore diameter and its hydrothermal stability.
4

5. MATERIALS AND METHODS
• Model Drugs
• SBA-15 Synthesis
• Nitrogen Physisorption and Calculations
• Drug Loading
• Determination of Drug Loading
• Thermogravimetric (TG) Analysis
• Differential Scanning Calorimetry (DSC)
• In Vitro Dissolution
5

6. Model Drugs
Carbamazepi
ne
cinnarizine danazol diazepam fenofibrate
griseofulvin indomethacin ketoconazole nifedipine phenylbutazon
e
6

7. MESOPOROUS SBA 15
7

8. SBA15 Synthesis
Aq HCL solution + 6g
Pluronic 123
15.5g Sod. Silicate +
45g de iodised water
Acidic P123 Solution Increase temperature to 90
℃ (48h)
Rinse with 200 ml of
deiodised water
Then silica powder
calcinated at 550 ℃ for 8 h
Stirred for 5 min
(Temp 35 ℃ for 24h)
Cooled & Flitered (0.47
micro membrane filter)
Dried at 40℃ (P= 10 -3
bar)
8

9. NITROGEN ADSORPTION–DESORPTION
ISOTHERM
DRUG LOADING
DRUG CONTENT DETERMINATION
TG ANALYSES DSC
9

10. IN- VITRO DISSOLUTION
DRUG CONTENT ASSAY PHYSICAL AND CHEMICAL
STABILITY
10

11. NITROGEN ADSORPTION–DESORPTION ISOTHERMS
• Nitrogen adsorption–desorption isotherms of the calcined SBA-15 powder were
recorded using a Micromeritics Tristar 3000-apparatus.
• Measurements were performed at -196℃ and all samples were pretreated at 300 ℃ for
12 h. under nitrogen flushing prior to analysis.
• The total surface area was calculated using the BET model in the relative pressure
range between 0.05 and 0.2.
• The total pore volume was estimated using the t-plot method of Lippens and Bhor.
• The pore size distribution was derived from the adsorption branches of the nitrogen
isotherms using the BJH model.
11

12. DRUG LOADING
• All model drugs were loaded onto SBA-15 according to the incipient wetness
procedure in order to obtain a drug loading of 20%.
• 150 mg of SBA-15 was impregnated with 750 ml of a 50 mg/ml drug solution in
methylene chloride.
• The moist powder was homogenized with a spatula until seemingly dry, after which it was
dried further at 40℃, under reduced pressure (103 bar) in a vacuum oven (Heraeus) for
48 h to remove any residual methylene chloride.
12

13. Drug Content Determination
• The drug content of the SBA-15 formulations was determined by suspending 5 mg of
drug-loaded powder in 10 mL of an aqueous solution containing 3% of sodium lauryl
sulfate.
• These suspensions were sonicated for 30 min, and subsequently put in a rotary mixer
for 24 h.
• Preliminary tests had pointed out that a time span of 24 h was sufficient to remove the
entire drug load from the SBA-15 pores.
• The silica was separated from the drug solutions using a PTFE-membrane filter (0.45
mm).
• All analyses were performed in triplicate. The mean values obtained from these
experiments were used to calculate the maximum drug release in the in vitro dissolution
experiments.
13

14. Thermogravimetric Analysis
• TG analyses were performed on a TGA Q-500 apparatus.
• The balance purge consisted of pure nitrogen (10 mL/min).
• Pure oxygen was used as the sample purge gas (90 mL/min).
• TG runs were recorded from 30 to 800℃ at a heating rate of 10 ℃ /min. The drug content
was calculated by correcting the weight loss of the SBA-15 formulations between 100
and 750 ℃ for the weight loss of drug-free SBA-15 in the same temperature range.
• All experiments were performed in platinum pans.
14

15. DSC
• DSC experiments were performed on a TA Instruments Q-2000 DSC apparatus at a
heating rate of 28 ℃ /min.
• Dry nitrogen at a flow rate of 50 mL/min was used as the purge gas through the DSC cell.
• Sample weights varied between 5 and 8 mg. The temperature scale was calibrated with
benzoic acid, tin, and indium standards. The latter was used to calibrate the enthalpic
response as well.
15

16. IN-VITRO DISSOLUTION
• Drug release from the SBA-15 formulations was compared to that of their corresponding
crystalline materials and drug-SBA-15 physical mixtures.
• All dissolution tests were carried out at ambient temperature. Twenty milliliters of release
medium was added to a glass vial containing 20.1 mg of drug, under the form of either an
SBA-15 formulation, a physical mixture or as the crystalline material.
• One milliliter samples were withdrawn with asyringe at 5, 10, 30, and 60 min, PTFE
membrane filter and immediately replaced with 1 mL of fresh medium.
• Most of the dissolution experiments were conducted in simulated gastric fluid without
pepsin (SGFsp, USP 24, pH 1.2).
• In order to allow for better discrimination between physical mixtures and formulations,
pure water was selected as the release medium for these three compounds.
16

17. DRUG QUANTIFICATION
• All samples coming from the drug content assay and the in vitro dissolution experiments
were analyzed by UV-spectrometry in a Tecan Infinite M200 microplate reader using flat
bottomed transparent 96 well plates.
• The standards used to construct the calibration curves were prepared in the same
media used for the experiments.
• Sample concentrations were calculated by interpolation from the calibration curve
response using a liner regression model.
• All calibration curves were linear over a concentration range between 2.5 and 100
mg/mL.
17

18. PHYSICAL AND CHEMICAL STABILITY
• The physical and chemical stability of the SBA-15 formulations upon storage was
evaluated by storing replicates of each formulation for 6 months in a desiccator at 258 ℃
/52% RH (saturated Mg(NO3)26H2O solution).
• Drug-free SBA-15 powder was stored under the same conditions.
• After storage, the UV-spectra, DSC thermograms and in vitro release profiles were
recorded again.
• The stored drug-free SBA-15 was again subjected to nitrogen gas adsorption.
18

19. RESULT AND DISSCUSSION
19

20. Does Drug Loading process effected drug/SBA15 Stability?
• The nitrogen physisorption results summarized in next slide illustrate that both batches of SBA-15
used throughout this study exhibited similar characteristics.
• UV Spectra of aqueous solutions obtained after suspending freshly prepared SBA15
formulations were perfectly similar to as received drugs.
20

21. Batch 1 Batch 2
Freshly
Prepared
After Storage Freshly
Prepared
After Storage
Average pore
diameter (nm)
7.6 7.5 8.3 8.4
Surface area
(m2/g)
635.5 557.8 663.5 628.5
Total pore
volume
(cm3/g)
0.81 0.76 0.83 0.82
Micropore
volume
(cm3/g)
0.10 0.07 0.12 0.09
PHYSICAL PARAMETERS
21

22. Drug Content (%)
Compound TG
Carbamazepine 22.5
Cinnarizine 20.7
Danazol 20.9
Diazepam 21.7
Fenofibrate 21.5
Griseofulvin 19.7
Indomethacin 18.6
Ketoconazole 20.4
Nifedipine 20.7
Phenylbutazone 19.8
DRUG CONTENTS OF THE SBA-15 FORMULATIONS,
AS DETERMINED VIA TG (N=1)
22
In addition, TG results indicated that
the drug-free SBA-15 powder lost 4.1 ±
0.9% of its weight in the region below
100℃, whereas none of the
formulations lost more than 1.6%.

23. In-Vitro Dissolution (Pharmaceutical Performance)
23

24. Does Drug-Silica Interactions of different compounds effect drug release?
• We hypothesize that interactions between hydrophobic drug molecules and the silanol groups
covering the silica surface are not a major factor influencing drug release.
• The rate limiting step for drug release will rather be the time needed for diffusion out of the internal
pore network.
Does Water, Acidic media, SGF effect silica?
The short experiment time (1 h) and the low solubility of SBA-15 in water and acidic media such as
SGFsp rule out the effect of matrix erosion on drug release.
24

25. DSC THERMOGRAMS
DSC of Indomethacin DSC of Carbamazepine
25

26. CONCLUSION
Generic solvent
impregnation method
was successful
In all cases, absorbed
fraction Was non
crystalline
Physical properties and
pharmaceutical
performance was retained
after 6 months of storage
Encapsulation in SBA-15 can be
applied as a dissolution enhancing
formulation approach for a very wide
variety of poorly soluble drugs.
SBA-15 to yield physically stable,
dissolution enhancing
formulations, irrespective of a
drug’s physicochemical profile
Relatively low cost of SBA15
synthesis and simplicity of
drug loading process
26

27. REFRENCE
Speybroeck, Michiel Van, et al. “Ordered Mesoporous Silica Material SBA-15: A Broad-Spectrum Formulation
Platform for Poorly Soluble Drugs.” Journal of Pharmaceutical Sciences, vol. 98, no. 8, Aug. 2009, pp. 2648–
2658, 10.1002/jps.21638. Accessed 9 Apr. 2021.
27

28. THANK YOU
28