This document discusses several recent studies on enhancing the oral delivery of celecoxib (CLX/CEL), a poorly water soluble drug. Three key approaches explored are: 1. Developing CLX nano crystalline solid dispersions using stabilizers like PVP and SDS, which showed improved particle distribution and stability. 2. Using a dry elixir formulation with ethanol and water to quickly dissolve CLX and enhance bioavailability. 3. Creating a DMSO solvate of CEL that demonstrated better flowability and tabletability than commercial Form III in a direct compression tablet. The studies demonstrated various formulations and techniques, like liquisolid technology, bead milling nanoparticles, and lipid-based systems,

1. Preformulation and
Recent Research Apps
of celecoxib
L a b 1 / r o u n d 3
U n d e r S u p e r v i s i o n
D r s a r a s o l i m a n
D r s h e r e e n s a m e h

2. Physicochemical parameters
Chemical properties
• Chemical Formula : C17H14F3N3O2S
• IUPAC Name :
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H
-pyrazol-1-yl]benzene-1-sulfonamide
• Molecular Weight : 381.4
• Monoisotopic Mass : 381.07588236
• Hydrogen Bond Donor Count : 1
• Hydrogen Bond Acceptor Count : 7
• Rotatable Bond Count : 3
• Complexity : 577
Physical properties
• Color / form : pale yellow solid
• Melting Point : 529.0±60.0
• Boiling Point : 157-159
• Solubility : Poorly soluble “In water, 4.3
mg/L at 25 °C”
• Vapor Pressure : 1.19X10-9 mm Hg at 25
°C
• pKa : 11.1
• LogP : 3.53

3. Stability aspects
• For capsule dosage form
Stability data on the product are provided for 4 pilot-scale batches of each capsule
strength stored at 25°C/60% RH (12 months) and 40°C/75% RH (6 months). Ther
e are No clear changes or trends were observed. All parameters remain within the
specified limits at accelerated and long-term storage conditions.
• So the proposed shelf-life of 2 years is acceptable
• Photostability studies showed that the capsules are not sensitive to light.
• For Suspension dosage form packaged in amber PVC bottles were stable for up to
93 days when stored at 5°C or 23°C.
• also shelf-life could be enhanced by Nano emulsion formulation to become 2.38
years.

4. Celecoxib overview
• Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) used to
treat pain and inflammation associated with various conditions such as
arthritis, menstrual cramps, and acute pain.
• It works by blocking the production of PGs, which are r esponsible for
causing pain and inflammation in the body. Unlike other NSAIDs, CEL
selectively inhibits the COX-2 enzyme, which is responsible for producing
prostaglandins in response to injury or inflammation, while sparing the
COX-1 enzyme, which plays a protective role in the stomach lining and
blood clotting. This makes CEL a safer option for long-term use in patients
with a history of gastrointestinal bleeding or cardiovascular disease.
• CEL is available in capsule form for oral administration, but a new tablet
formulation has been developed to improve its flowability, tabletability,
and release properties.

5. Ahmed Ibrahim 18006
Conclusion
CLX-NC was successfully prepared using the chosen
PVP VA64 and SDS as the combined stabilizers, and
optimized, using a central composite ,was found to have
an adequate particle distribution and no substantial
crystalline change occur. Quality evaluation indicated
that CLX-NC could provide excellent physical stability
during six months’ storage
Journal Name
pharmaceutics
Year of publication
2019
Delivery system
Solid Dispersions compressed tablet
Excipients
Celecoxib (CLX), used as micronized crystallin
e power, was purchased from Yijing Industrial
Co. Ltd. Hydroxypropylmethylcellulose acetate
succinate and hydroxypropylcellulose. Polyviny
lpyrrolidone—polyvinyl acetate copolymers and
polyvinylpyrrolidone were generouslyprovided b
y BASF. Sodiumdodecyl sulfate (SDS), used a
ssecondary stabilizer. Milli-Q water.
Aim to
Enhanced Oral
Bioavailability of Celecoxib
Nano crystalline Solid
Dispersion based on Wet
Media Milling Technique:
Formulation,Optimization
and In Vitro/In Vivo
Evaluation
to develop and optimize CLX nano crystalline
(CLX-NC) solid dispersion prepared by the wet
medium milling technique combined with
lyophilization to enhance oral bioavailability

6. Ahmed Hamdy Ali 1015
Conclusion
We have studied the crystal growth kinetics of amo
rphous CEL both on the surface and in bulk. Upon
cooling, the crystal growth rates near and below Tg
(51.8 °C)for both surface and bulk form III CEL abr
uptly increased from those predicted from diffusion
-controlled crystal growth mechanism, The nearly 8
0-fold increase in the surface growth rate of CEL fo
rm III crystal over bulk growth in the glassy region i
s attributed to the fast molecular surface diffusion.
Journal Name
Crystal growth design
Year of publication
2019
Delivery system
a solid dispersion system
Excipients
Form III CEL was purchased from
Aarti Drugs Pvt Ltd.(Mumbai, India)
and used as received.
Aim to
Crystal Growth of
Celecoxib from Amorphous
State: Polymorphism,
Growth Mechanism, and
Kinetics
The crystal growth kinetics of amorphous Celecoxib
(CEL), was systematically investigated for
developing effective stabilization strategies to
enhance solubility of CEL.

7. Ibrahim saad 18003
Conclusion
new development of solid formulation for celecoxib is still
desirable. Dry elixir (DE) formulation is an efficient
dosage form for oral delivery to circumvent problems
such as low solubility, dissolution and bioavailability of
BCS class drug II.9–11 The loaded materials in the DE
system are very quickly dissolved in GI media due to the
cosolvent effect of ethanol and water, resulting in both an
enhaned dissolution and oral bioavailability
Journal Name
journal of Nanoscience and Nanotechnology
Year of publication
2019
Delivery system
dry elixir system
Excipients
Celecoxib- ethanol – Water – dextrin – sodium –
lauryl sulfate
Aim to
Improved
Dissolution
and Oral
Bioavailability
of Celecoxib
by a Dry Elixir
System
Enhancing the dissolution rate and oral bioavailability of
celecoxib. DE system has been used for improving
solubility, oral bioavailability of poorly water-soluble
drugs.

8. Ibrahim sherif 18004
Conclusion
development of a solid dispersion system to improve
patient compliance and safety with respect to poorly
water-soluble celecoxib (CXB)
Journal Name
pharmaceutics
Year of publication
2019
Delivery system
solid dispersion system
Excipients
CXB and SPAN 80 .Cremophor RH40, Poloxamer 188,
Poloxamer 407, and Soluplus . Labrafac PG, Labrafil M
1944 CS, Labrasol, Plurol Oleique CC497, and Transcut
ol HP were obtained from Gattefosse . Ryoto sugar ester
L-1695 and P-1670 were kindly provided by Mitsubishi-K
asei Chemical Co. Heweten 101 (microcrystalline cellulo
se) and Pharmatose 200M (Lactose)
Aim to
Development and
Evaluation of Poorly Water
-Soluble Celecoxib as Solid
Dispersions Containing
Nonionic Surfactants Using
Fluidized-Bed Granulation
to develop a solid dispersion system with improved
dissolution, absorption, and patient compliance of poorly
water-soluble celecoxib (CXB)

9. Ahmed ismail 18009
Conclusion
developing a direct compression tablet formulation of CEL
using the DMSO solvate of CEL, which exhibits better flow
ability and tabletability than the commercial Form III CEL.
CEL also releases more quickly from the tablet than CEL c
apsules. The formulation develops a predictive techniques
for assessing powder flowability and tableting performance.
This study exemplifies the benefits of combining crystal en
gineering and materials science to enable the efficient dev
elopment of high quality tablet products.
Journal Name
International Journal of pharmaceutics
Year of publication
2021
Delivery system
Direct compress ion tablet
Excipients
- Celecoxib - DMSO - FMC Biopoly
mer –Philadelphia - Mannitol - SLS
- Mg St
Aim to
Direct compression tablet
formulation of celecoxib
enabled with a
pharmaceutical solvate
Improve flow and denisty of DC tablet
celecoxib by adding (DMSO) solvate

10. Apadeer shenoda 18001
Conclusion
The results show that Liquisolid technology Combined
with ball milling is an efficient tool for enhancing the
dissolution of poorly water soluble drugs
Journal Name
Journal of pharmaceutical innovation.
Year of publication
2022
Delivery system
Classic Liquisolid
Excipients
* PVP * Micro crystaline cellulose * Silica
Aim to
Combining liquid and
cogrinding technique to
enhance the dissolution
rate of celecoxib
Enhance the dissoluti on rate of poorly water soluble drugs .

11. Abrar osama 18008
Conclusion
. The formulation of celecoxib enhanced by using Bead Mil
ling method as an useful equipment for the preparation of
the nanoparticles in nano-scale form. It has enhanced diss
olution profiles of over 80 times comparing to micron sized
celecoxib powder, leading to improved bioavailability and i
n vitro dissolution and oral absorption of lipophilic drugs
Journal Name
Journal of Nanoscience and Nanotechnolo gy
Year of publication
2019
Delivery system
Nanosus pension
Excipients
Celecoxib Tween80 -HPMC -Dow Chemical
Aim to
Preparation and
Characterization of
Celecoxib Nano suspension
Using Bead Milling
The aim of this study is to develop Nano suspension fo
r improved dissolution of poorly water soluble celecoxi
b

12. Ahmed Elgamal 18014
Conclusion
The present study demonstrated that at equivalent lipid do
ses, increasing the drug saturation above equilibrium solu
bility resulted in an increased in vivo bioavailability of celec
oxib from single component LBDDS relative to the corresp
onding nonsupersaturated LBDDS. Using the in vitro Perm
eapadR model, while supersaturation in LBDDS did not re
veal higher flux across the biomimetic membrane
Journal Name
European Journal of Pharmaceutical Sciences
Year of publication
2020
Delivery system
Lipidbased drug delivery systems
Excipients
buprofen Capmul MCM C8 Maisine CC Labrasol ALF
Porcine pancreatic lipase 4x USP, calcium chloride dih
ydrate CaCl2⋅2H20, 4- bromophenylboronic acid (4- B
BBA) and maleic acid
Aim to
Exploring impact of
supersaturated lipid based
drug delivery systems of
celecoxib on in vitro
permeation across
Permeapa dR membrane
and in vivo absorption
to explore supersaturat ed versus nonsupersaturat ed li
pidbased systems at equivalent lipid doses, on in vivo bi
oavailabilit y in rats and on in vitro permeation across a
biomimetic Permeapad R membrane to establish a pote
ntial in vivo - in vitro correlation.

13. Amir nageh 18007
Conclusion
In a ternary ASDs consisting of CEL, CoPVP, and TP
GS, the presence of CEL improved the miscibility bet
ween TPGS and CoPVP. TPGS improved the propert
ies of CEL ASDs during dissolution by enhancing the
powder wetting and by facilitating the formulation of C
EL nanoparticles. CEL ASDs containing 20% TPGS d
emonstrated the fastest dissolution and the highest d
egree of supersaturation in both non-sink
Journal Name
Journal of Drug Delivery Science and Technology.
Year of publication
2019
Delivery system
Amorphous solid dispersions.
Excipients
Copovidone. polyethylene glycol 1000 succinate..To
copherol
Aim to
Effect of surfactant level
on properties of celecoxib
amorphous solid
Dispersions.
to explore the influence of Dα-tocopheryl polyethylen
e glycol 1000 succinate (vitamin E TPGS) on the pro
perties of celecoxib (CEL) amorphous solid dispersio
ns (ASDs).

14. Ahmed sahry 18017
Conclusion
a novel CEL IR tablet was formulated using CEL-ADI
EM solid dispersion with the help of JMP® by a QbD
approach. The choice of disintegrants used in the for
mulation was statistically proven to significantly affect
the performance of tablets; this is a case study which
set an example to follow for many further applications
of the QbD approach and of statistics in designing
new pharma products
Journal Name
pharmaceutics
Year of publication
2022
Delivery system
solid dispersion
Excipients
Lactosemon ohydrate (75%) & microcrystal linecellulo
se (25%) - crosslinkedP VP - Mgstearate - crosslinked
NaCMC - SLS
Aim to
Synthesis of Celecoxib
Eutectic Mixture Particles
via Supercritical CO2
Process and Celecoxib
Immediate Release Tablet
Formulation by Quality by
Design Approach
Developed a therapeutic eutectic system for CEL whic
h is a promising approach for oral delivery to enhance
bioavailability

15. Asmaa alaa
Conclusion
The MDDS tablet allowed microwave, stimultane
ously maintaining the structural and geometric int
egrity of the tablets and in situ amorphisation perf
ormance
Journal Name
European jurnal of Pharmaceutics and Biopharmaceutica
Year of publication
2022
Delivery system
tablet
Excipients
Celecoxib PVP -HPMC -VA Microcrystalline Cellulose
Mannitol Crospovidone Mg st NaH2 Po4,
Aim to
Development of a multi
particulate drug delivery
system for in situ
amorphisation
The aim of this study is to develop drug delivey system
of poor watersoluble colocxibe by multiparticulate drug
delivey in situ amorphisation

16. Conclusion
• To enhance oral CLX bioavailability , celecoxib nano crystalline was
prepered using PVP VA64 and SDS as the combined stabilizers, and
optimized, using a central composite, was found to have an adequate
particle distribution and no substantial crystalline change occur.
• using dry elixir formulation, this form of oral delivery is efficient and
helps solve issues with low solubility, dissolution, and bioavailability.
• A new tablet formulation of CEL was developed using DMSO solvate,
with better flowability and tabletability than commercial Form III CEL.
• Liquisolid technology Combined with ball milling is an efficient
tool for enhancing the dissolution of poorly water soluble drugs.
• development of a solid dispersion system to improve patient
compliance and safety with respect to poorly water-soluble CXB

17. • By using Bead Milling method for the preparation of nanoparticles of
CLX , it has enhanced dissolution of CLX, leading to improve
bioavailability and oral absorption of lipophilic drugs.
• The materials are very quickly dissolved by the cosolvent effect
of ethanol and water, resulting in both an enhaned dissolution
and oral bioavailability.
• The nearly 80-fold increase in the surface growth rate of CEL
form III crystal over bulk growth in the glassy region is attributed
to the fast molecular surface diffusion.
• The choice of disintegrants used in the formulation was proven to
significantly affect the performance of tablets.
• TPGS improved the properties of CEL ASDs during dissolution by
enhancing the powder wetting and by facilitating the formulation of
CEL nano particles.

18. • At equivalent lipid doses, increasing the drug saturation above
equilibrium solubility resulted in an increased in vivo bioavailability of
celecoxib from single component LBDDS relative to the corresponding
nonsupersaturated LBDDS.
• The MDDS tablet allowed microwave, stimultaneously maintaining th
e structural and geometric integrity of the tablets and in situ amorphi
sation performance.

19. Designed by:
Ahmed Ibrahim
Ahmed Hamdy
Abadeer shenoda
Amir nageh
Thank you