Dissertation Proposal
Anwana, Ndifreke U.
PHA/F/22/23/0005
JUNE 22, 2024
Topical Nanoemulsion Delivery System for Ketoprofen Using Shea Butter
1. Introduction
1.1 Background and Rationale
- Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) commonly
used for its
analgesic and anti-inflammatory effects (Patel et al., 2012).
- Traditional administration routes of ketoprofen, such as oral or
intravenous, can cause
gastrointestinal irritation and systemic side effects (Grosser et al., 2011).
- The development of a topical nanoemulsion delivery system can
potentially reduce
these side effects while enhancing drug bioavailability and patient
compliance.
1.2 Shea Butter as a Carrier
- Shea butter, derived from the nuts of the Shea tree (Vitellaria paradoxa),
is widely
recognized for its moisturizing and anti-inflammatory properties (Maranz et
al., 2004).
- It is rich in fatty acids and antioxidants, which can improve drug
solubilization and skin
penetration (Ahmad et al., 2010).
1.3 Nanoemulsion Technology
- Nanoemulsions are colloidal dispersions with droplet sizes typically
ranging from 20 to
200 nm, providing enhanced drug delivery through improved solubility and
skin
permeability (Komaiko ; McClements, 2016).
- These systems offer potential advantages such as controlled release,
protection of the
active pharmaceutical ingredient, and improved stability (Gutiérrez et al.,
2008).
2. Objectives
2.1 Main Objective
- To develop and characterize a topical nanoemulsion delivery system for
ketoprofen
using Shea butter as a carrier.
2.2 Specific Objectives
1. To formulate a stable nanoemulsion incorporating ketoprofen and Shea
butter.
2. To evaluate the physicochemical properties of the developed
nanoemulsion.
3. To assess the in vitro and ex vivo skin permeation and retention of
ketoprofen from
the nanoemulsion.
4. To investigate the anti-inflammatory efficacy of the topical nanoemulsion
in
appropriate models.
3. Literature Review
3.1 Existing Drug Delivery Systems for Ketoprofen
- Overview of currently available administration forms of ketoprofen and
their limitations
(Barthel et al., 2000).
3.2 varieties of shea butter and properties
3.3 Proximate Analysis?
3.4 Role of Shea Butter in Topical Formulations
- Examination of Shea butter, its composition and its benefits in skincare
and drug delivery
(Zeng & Zhao, 2018).
3.3 Nanoemulsion Technology
- Detailed discussion on the principles and applications of nanoemulsions
in drug delivery (Salvia-Trujillo et al., 2013).
4. Methodology
4.1 Formulation Development
- Selection of appropriate surfactants and co-surfactants for nanoemulsion
preparation.
- Optimization of the formulation using factorial design.
4.2 Physicochemical Characterization
- Particle size and distribution analysis (Dynamic Light Scattering, DLS).
- Zeta potential measurement for stability assessment.
- Rheological studies to evaluate viscosity and flow properties.
4.3 In Vitro and Ex Vivo Studies
- In vitro release studies using dialysis membrane techniques.
- Ex vivo skin permeation studies using Franz diffusion cells and excised
human/animal
skin.
4.4 In Vivo Anti-inflammatory Studies
- Assessment of anti-inflammatory effects in an animal model of
inflammation.
5. Expected Outcomes
- Enhanced skin permeation and retention of ketoprofen.
- Improved stability and controlled release profile of the nanoemulsion.
- Demonstrated anti-inflammatory efficacy with reduced systemic side
effects.
6. Significance of the Study
- Development of an effective and patient-friendly topical delivery system
for ketoprofen.
- Contribution to the broader field of nanoemulsion-based drug delivery
systems
7. Timeline
- A detailed timeline outlining the proposed schedule for research activities
is yet to be determined
8. Budget
- A comprehensive budget estimate covering materials, equipment, and
other researchrelated expenses.
9. References
- Include all the references cited in the proposal in an appropriate citation
style. For
instance:
Barthel, C., Stewart, S. F., & Wagner, B. (2000). Ketoprofen: Overview of
Pharmacology
and Current Approaches to Improved Delivery. *Clinical Drug Investigation,
19*(1), 1-36.
Grosser, T., Smyth, E., FitzGerald, G. A. (2011). Anti-inflammatory,
antipyretic, and
analgesic agents; pharmacotherapy of gout. In *Goodman & Gilmans: The
Pharmacological Basis of Therapeutics* (12th ed.).
Maranz, S., Wiesman, Z., Bisgaard, J.; Bianchi, G. (2004). Germplasm
resources of
*Vitellaria paradoxa* based on variations in fat composition across the
species
distribution range. *Agroforestry Systems, 60*(1), 71-76.
Ahmad, M., Madani, S. Ahmed, M. I. (2010). Pharmaceutical applications of
shea fat
in topical preparations. *Journal of Dermatological Treatment, 21*(1), 5260.
Komaiko, J., McClements, D. J. (2016). Formation of food-grade
nanoemulsions
using low-energy preparation methods: A review of available methods.
*Comprehensive
Reviews in Food Science and Food Safety, 15*(3), 331-352.
Gutiérrez, J. M., González, C., Maestro, A., Solè, I., Pey, C. M., Nolla, J.
(2008).
Nano-emulsions: New applications and optimization of their preparation.
*Current Opinion in Colloid Interface Science, 13*(4), 245-251.
Salvia-Trujillo, L., Rojas-Graü, M. A., Soliva-Fortuny, R., Martín-Belloso, O.
(2013).
Physicochemical characterization of food-grade emulsions and
nanoemulsions
prepared with different emulsifiers using ultrasonic energy. *Food
Hydrocolloids, 30*(1),
118-126.
Zeng, S., Zhao, L. (2018). Shea butter: A beneficial oil for topical and
systemic uses.
*Journal of Ethnopharmacology, 217*, 100-110.
Optimization of topical nanoemulsion:
Optimizing a nanoemulsion using Shea butter for topical analgesic delivery
can be achieved through a design of experiments (DoE) approach.
using the Box-Behnken design:?
1. objectives:
a. Maximize analgesic loading,
b. Maximize stability, and skin permeation
c. Minimize particle size.
2. Select factors:
a. Shea butter concentration (A),
b. surfactant concentration (B),
c. oil phase ratio (C),
d. homogenization speed (D).
3. Choose levels:
- A: 5%, 10%, 15% (w/w)
- B: 1%, 2%, 3% (w/w)
- C: 20%, 30%, 40% (v/v)
- D: 5000, 10000, 15000 rpm
4. Design the experiment:
- Use software (e.g., Minitab, Design-Expert) to generate a Box-Behnken
design.
5. Conduct the experiments:
- Prepare nanoemulsions according to the design matrix.
- Characterize particle size, zeta potential, and analgesic loading.
- Evaluate skin permeation using Franz diffusion cells.
6. Analyze and model the data:
- Use response surface methodology (RSM) to fit quadratic models for
each response.
- Identify significant factors and interactions.
7. Optimize the nanoemulsion:
- Use numerical optimization or desirability functions to find the optimal
conditions.
- Validate the optimized formulation experimentally.