Formulation And Evaluation of Topical Polymeric Gel For The

Management of Inflammation And Pain

THESIS PRESENTATION
OF
MASTER OF PHARMACY
(PHARMACEUTICS)
BY
MANVEER SINGH
Regd. No. UIP/F-047

SUPERVISOR CO- SUPERVISOR

DR. VINEY CHAWLA DR. HONEY
Professor and Principal Associate Professor and
UIPSR, BFUHS, Head
Faridkot UIPSR, BFUHS, Faridkot

UNIVERSITY INSTITUTE OF PHARMACEUTICAL SCIENCES AND RESEARCH,

BABA FARID UNIVERSITY OF HEALTH SCIENCES, FARIDKOT
 Contents
Introduction
Rationale of the Study
Aims of the Study
Plan of the Work
Materials and Methods
Results and Discussion
Summary & Conclusion
Achievements
 Introduction
• Inflammation: Immune response to tissue injury or infection, driven by
mediators .
• Global Impact: Inflammation and pain affect millions globally, contributing
to disability, decreased productivity, and rising healthcare costs.
• Prevalent Conditions: Major conditions like rheumatoid arthritis,
inflammatory bowel disease, and COPD affect over 1.7 billion people
globally, especially in low- and middle-income countries.
• Opioid Crisis: Increased opioid-related deaths highlight the need for better
pain management strategies, especially in countries with liberal prescribing
practices.
• NSAIDs: Inhibit COX enzymes, reducing prostaglandin synthesis and
alleviating pain/inflammation.
• Traditional NSAIDs: Effective but associated with gastrointestinal and
cardiovascular risks
• Most traditional NSAIDs are poorly water-soluble and good permeability
across biological membranes, allowing for effective absorption, but their low
solubility can limit bioavailability.
• Solid dispersion represents a promising strategy in pharmaceutical science for
enhancing the solubility, bioavailability, and therapeutic efficacy of poorly
water- soluble drugs.
 Rationale of the study
• Aceclofenac, classified as a BCS class II drug with 3.5µg/ml solubilty and log p 2.1 resulting in low
oral bioviavailbilty. Due to its poor solubility and bioavailability, the recommended daily dose of l
Aceclofenac for adults is 100mg – 200mg.

• Its topical absorption is hindered by limited dissolution in aqueous environments.

• Currently, no Solid dispersion deriver formulation is available except 1.5% w/w topical cream/gel,
primarily used treatment of Inflammation and pain like rheumatoid arthritis.

• Overcoming these challenges requires innovative formulation strategies tailored to enhance solubility,
permeability, and localized efficacy, while minimizing systemic exposure and variability in drug
response.

• The study aims to develop and evaluate a gel formulation of aceclofenac using solid dispersion with
biocompatible polymers for enhanced topical delivery, focusing on its biopharmaceutical performance
compared to commercially available formulations
 Drug characterstics
Class Pharmacokinitc Dosage Mechanisim of
action
Aceclofenac is a non- It is rapidly absorbed The recommended Mechanism of
steroidal anti- after oral dosage of Action:
inflammatory drug administration, aceclofenac for adults Aceclofenac
(NSAID) belonging achieving peak is typically 100 mg inhibits
to the phenylacetic plasma administered twice cyclooxygenase
acid derivative class. concentrations within daily, depending on (COX) enzymes,
1.25 to 3 hours, with the severity of the reducing
a half-life of 4-4.3 condition and patient prostaglandin
hours, and is response synthesis, which
primarily leads to decreased
metabolized in the inflammation, pain,
liver to its active and swelling in
metabolite, with inflammatory
excretion mainly via conditions.
urine.
 Aim and Objectve
• To formulate the solid dispersion based Aceclofenac Loaded Gel For The
Management Of inflammation and pain.

• To evaluate the successful batches of Aceclofenac gel against the

management of inflammation and pain.
 Plan of work
• Pre-formulation studies using FTIR and DSC to assess the morphology,
physicochemical properties, and drug-excipient compatibility of aceclofenac.
• Fabricated solid dispersions of aceclofenac to enhance solubility and bioavailability,
characterized through advanced techniques.
• Incorporated solid dispersions into a gel matrix, evaluating drug release, stability, and
viscosity to improve therapeutic efficacy in inflammation and pain management.
• In vitro assays demonstrated significant drug release of the aceclofenac gel
formulation, highlighting the benefits of solid dispersion technology.
 Aceclofenac and
biocompatible polymers (e.g.,

MATERIALS AND METHODS PVP K30, PEG 4000, Urea)

were chosen for solid
dispersion formulation.
API Polymers Excipients

Aceclofenac-loaded solid
Aceclofenac dispersions were prepared via
Poly vinyl pyrollidone Methanol solvent evaporation,
incorporating the drug into
polymers melted at 45-160°C.
Polyethylene
Phosphate Buffer
glycol
Carbopol 934 was soaked for 24
hrs in pH 5.5 buffer, neutralized
with 0.1N NaOH, and combined
Urea Glycerin with 0.4% w/v aceclofenac,
glycerin, and methylparaben,
forming a homogenous gel.

Solid dispersions were integrated

Carbopol 934 Methylparaben into a gel base. carbopol 934 and
mixed thoroughly to achieve the
desired pH, consistency, and
spreadability for topical
application.
 RESULT AND DISCUSION
Pre-formulation Studies
Organoleptic Properties Melting point
Table 1: Organoleptic properties of Aceclofenac Table 2: Melting point of Aceclofenac
Parameter Reference Observed
S. No. Properties Reference Observed

Melting Point 155.0°C- 160.11°C

1. Physical Solid, Solid, Crystalline 163.8°C
State Crystalline

2. Color off-white off-white The capillary tube method revealed that the
melting point of Aceclofenac is 160.11°C,
3. Odour Odorless Odorless
which indicating the purity of the drug
sample.
 Standardization of ACK by UV

Figure1: UV spectrum

UV Spectrum of ACK sample showed maximum absorption at 274nm which was

consistent with reference value.
 FTIR spectrum of Aceclofenac

Figure2: FTIR spectrum

The structure of Aceclofenac was identified from functional group thus sample was pure.
 Differential Scanning Calorimetry

Figure3 : DSC thermogram

DSC thermogram showed a sharp endotherm(indicating Amorphous state) at 160.11°C.

Consistent with the standard melting temperature, indicating sample purity.
 Development of UV Spectrophotometric Method for Estimation of
Aceclofenac
Phosphate buffer (pH 5.5) Methanol

1.0 1.0

f(x) = 0.0373096774193549 x − 0.0319225806451615

R² = 0.998183157575712 f(x) = 0.0348650537634409 x − 0.0180129032258065
0.8 0.8 R² = 0.999803863223397

Absorbance (nm)
Absorbance (nm)

0.5 0.5

0.3
0.3

0.0
0.0 0 5 10 15 20 25
0 5 10 15 20 25
Concentration (µg/ml) Concentration (µg/ml)

The standard calibration curve of aceclofenac in The aceclofenac stock solution in methanol showed
phosphate buffer pH 5.5 showed linearity between a maximum absorbance at 274 nm, with a standard
1.0 to 25 μg/ml with an R² value of 0.9982, calibration curve demonstrating linearity (R² =
complying with Beer-Lambert's Law. 0.9998) within the 1-25 μg/mL concentration range,
adhering to Beer-Lambert's Law.
Physical studies during storage at room temperature
Table 3. Drug solubility in melted solid lipids at temperature range of (45- 65 ℃)

Physical Change
Physical Mixture (1:1)
1D 14D 28D

White color powder

Aceclofenac: PVP
with few white particles

Aceclofenac: Urea White color powder with few white No change in No change in
particles color/odor color/odor

White color powder with few white

Aceclofenac: PEG 4000
particles

Aceclofenac exhibited high solubility in organic solvents but limited solubility in aqueous media, and storage
stability studies confirmed its compatibility with excipients, showing no significant physical changes over time.
 Drug Excipient Interaction Studies

Figure 5: XRD diffraction patterns of physical mixtures A)

Figure 4: FTIR of physical mixtures (1:1) A) Aceclofenac and PVP- Aceclofenac and Urea B) Aceclofenac and PEG 4000 C)
K30 B) Aceclofenac and PEG 4000 and C) Aceclofenac and Urea Aceclofenac and PVP- K30

The chemical compatibility of aceclofenac with the excipients PVP, Urea, and PEG 4000 was confirmed
through FTIR and X-RD studies, supporting their suitability for the development of SD formulations.
 Physicochemical Characterization of SD

Figure 6: FTIR spectrum solid dispersion (SDs) A) Figure 7: XRD of Solid dispersions A) Aceclofenac and PVP-
Aceclofenac and PVP-K30 B) Aceclofenac and PEG 4000 C) K30 B) Aceclofenac and PEG 4000 C) Aceclofenac and Urea
Aceclofenac and Urea

The X-RD studies confirmed the chemical compatibility of aceclofenac with the selected polymers, as
indicated by the retention of sharp intense peaks in all physical mixture samples.
 Percentage Yield and % Drug Content
100.000

75.000

50.000

25.000
11 12 13 11 12 13 11 12 13
SD SD SD SD SD SD SD SD SD
CK CK CK CP CP CP CU CU CU
A A A A A A A A A
% Drug Content % Yield

Figure 8: Percentage Yield and Percentage Drug Content of aceclofenac formulations

The drug content (89.5±0.48% to 96.13±0.51%) and percentage yield (88.21% to 98.44%) across
all aceclofenac SD batches demonstrated high yield and consistent drug content, unaffected by
changes in drug-polymer ratios.
Physical Attributes and In vitro gelling parameters
Table 4: Physical Appearance of SD Gel batches
Spreadability
Viscosity
Batch Code Homogeneity Consistency pH (cm)
(cps)

ACKSD11G √ √ 5.52±0.83 55302 6.8±0.8

ACKSD12G √ √ 5.83±0.47 64220 6.6±0.4

The optimized SD gel batches (ACKSD11G and ACKSD12G) exhibited suitable pH (5.52±0.83,
5.83±0.47) and viscosity (55302, 64220 cP) for topical application, ensuring effective drug
permeation and spreadability.
 In vitro drug release studies
100

% Cumulative Drug Release

75

50

25

0
0 2.5 5 7.5 10
Time (h)
ACF ACKPM11 ACKSD11G ACKSD12G AMF

Figure 9: Percent cumulative in vitro drug release studies for aceclofenac SD gel formulations
(ACKSD11G and ACKSD12G) w.r.t. marketed formulation (MF) (n=3; mean ± S.D.)
The SD gel formulations (ACKSD11G and ACKSD12G) demonstrated significantly
higher and more consistent drug release (>90% within 8 hours) compared to plain
aceclofenac (ACF) and the marketed formulation (AMF
 Drug release, kinetic models and mechanism
Table 9: Correlation coefficients (R2) and release exponent (n) values obtained from the different
kinetic models for finally optimized aceclofenac-SD gels
ACKSD11G ACKSD12G
Kinetic Model
R2 n R2 n

Zero order 0.7098 5.61 0.7382 5.89

First order 0.9266 -0.1231 0.974 -0.1489

Higuchi 0.6891 39.23 0.5892 44.921

Korsemeyer-Peppas 0.8431 0.630 0.9173 0.475

The kinetic evaluation of optimized SD gel batches revealed that aceclofenac

followed first-order release kinetics with a predominantly diffusion-controlled drug
release mechanism.
 Summary & Conclusion
•The melting point of aceclofenac was determined to be 160.11°C, indicating purity, and FTIR analysis
confirmed the drug's integrity through characteristic absorption bands.
•A validated UV spectroscopy method demonstrated strong linearity for aceclofenac concentrations in both
methanol and phosphate buffer, ensuring reliable dosage measurement.
•Aceclofenac showed limited solubility in water and phosphate buffer but higher solubility in organic
solvents like methanol, highlighting the need for innovative formulations.
•Compatibility assessments revealed no significant changes in aceclofenac when mixed with various
polymers over time, indicating stability and suitability for formulation.
•The optimized solid dispersion gel batches (ACKSD11G and ACKSD12G) released over 90% of the drug
within 8 hours, outperforming plain aceclofenac (45%) and physical mixtures (60%), with stability
confirmed by accelerated tests at 40°C/75% RH for 3 months showing no significant changes.
 Achievements

Publications 1. A Review paper- Singh H, Singh M, Singh

N, Jain H, Goel H, Chawla V. Unraveling the therapeutic
prospects of Solid Lipid Nanocarriers for the treatment of
parasitic diseases. Int. J. Drug Deliv. Technol. 2024;
14(1):1-17.
2. A Research paper - Singh M, Goel H, Chawla V.
Development of Aceclofenac loaded Polymer Dispersion
Systems for the Management of Topical Inflammation and
Pain”- Communicated
Presentations
• 8 th International Symposium on Current Trends in Drug Discovery Research Ageing Associated Metabolic
& CNS Disorders, CSIRCentral Drug Research Institute, Lucknow, India (March 12-14, 2022)
• Theme- Digital Health Landscape in India- The need of the hour, VivekanandaGlobal University, Jaipur,
India (Nov 18-19, 2022)
Certifications
• GOOD CLINICAL PRACTICE CERTIFICATION of NIDA Clinical Trial Network (3rd March 2022)

Workshops
• Hands-on-workshop on "Computational Structure Based DrugDesign" organized in collaboration with
Schrodinger" Organized by ISFCP, Moga, Punjab.(24 jan 2022) 2) IBRO Supported Meeting and
Workshop on “ Recent Progress In Brain Research And Drug Delivery” Organized by ISFCP, Moga,
Punjab.(13th -15th may 2022)
Thanks