1. M.R. COLLEGE OF PHARMACEUTICAL SCIENCES
AND RESEARCH
Presented
By
SUJOY SASMAL
B.PHARM
4TH
YEAR, 8TH
SEMESTER
ROLL NO- 36301920008
REGISTRATION NO-203630201910053
PROJECT WORK
On
AN APPROACH TO ENHANCE SOLUBILITY BY DIFFERNENT
SOLUBILITY ENHANCEMENT TECHNIQUE
Under The Guidance
Of
DR. NANCY KAHALI(Associate professor)
2024-2025, MRCPSR
2. SL. NO TOPIC PAGE
NO
1 ABSTRACT 3
2 INTRODUCTION 4
3 LITERATURE REVIEW 5
4 AIM & RATIONALE 6
5 PHYSICAL APPROACH TO ENHANCE SOLUBILITY 7-21
6 TYPES OF SOLID DISPERSION & ELABORATION 8-21
7 SOLID DISPERSION : HOT MELT EXTRUSION FOR IBUPROFEN 14-18
8 SOLID DISPERSION : SOLVENT EVAPORATION FOR IBUPROFEN 19-21
9 CHEMICAL APPROACH TO ENHANCE SOLUBILITY 23-24
10 MISCELLANEOUS APPROACH TOENHANCE S0LUBILITY 25-26
11 CONCLUSION 27
12 REFERENCE 28-29
3. INTRODUCTION
Why do some drugs fail to work effectively?→ Poor water solubility limits absorption and
bioavailability.
What percentage of new drug candidates are poorly soluble?→ Nearly 40–70% of APIs face
solubility issues.
How can we overcome this barrier?→ By using solubility enhancement techniques.
What will we learn?→ Methods, mechanisms, and benefits of improving solubility.
What challenges do poorly soluble drugs present in formulation?→ They often result in low
bioavailability, erratic absorption, and therapeutic failure.
4. LITERATURE REVIEW
• Vemula et al., (2010) comprehensively review solubility enhancement techniques for poorly water-soluble drugs. The article explores physical and
chemical methods, including particle size reduction, solid dispersions, complexation, and micellar solubilization. It emphasizes their pharmaceutical
importance in improving bioavailability, aiding drug formulation, and enhancing therapeutic efficacy in modern drug development.
• Thorat et al., (2011) present a detailed review of conventional and novel solubility enhancement techniques for poorly soluble drugs. They discuss
methods like solid dispersions, complexation, nanotechnology, and supercritical fluid processing. The review highlights advancements in drug delivery
systems aimed at improving solubility, dissolution rate, and overall bioavailability.
• Jagtap et al., (2018 ) review various solubility enhancement techniques to improve the bioavailability of poorly water-soluble drugs. The article covers
conventional methods like micronation and solid dispersions, as well as advanced approaches such as nanotechnology. It emphasizes the role of these
techniques in effective pharmaceutical formulation and therapeutic performance.
• Kumar et al., (2016) provide a comprehensive overview of techniques to enhance drug solubility, a key factor in bioavailability. The review covers
physical, chemical, and biological methods, including solid dispersion, micronization, and complexation, emphasizing their importance in
pharmaceutical development for improving therapeutic efficacy of poorly soluble drugs.
5. • Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. International journal of pharmaceutical sciences review
and research. 2010 Nov;5(1):41-51
• Kumar S, Singh P. Various techniques for solubility enhancement: An overview. The Pharma Innovation. 2016;5(1, Part A):23.
• Kim KT, Lee JY, Lee MY, Song CK, Choi J, Kim DD. Solid dispersions as a drug delivery system. J Pharm Investigation
2011;41(3):125-42. Doi: 10.4333/KPS.2011.41.3.125
AIM : The main goal of solubility enhancement techniques is to enhance the dissolution rate and aqueous
solubility of Ibuprofen, thereby increasing their bioavailability and ensuring consistent clinical performance.
THE RATIONALE BEHIND THE AIM:
• Overcoming Bioavailability Barriers for Ibuprofen.
• Achieving Consistent Therapeutic Efficacy of Ibuprofen.
• Reducing Dosage Variability Ibuprofen.
• Supporting Patient Compliance and Safety Ibuprofen.
• Optimizing Manufacturing Processes Ibuprofen.
6. TECHNIQUES INVOLVING OF AN APPROACH TO ENHANCE SOLUBILITY BY DIFFERENT
SOLUBILITY ENHANCEMENT TECHNIQUES :
PHYSICALAPPROACHES :
A) Particle Size Reduction:
• Micronization: Reduces particle size to increase surface area, enhancing dissolution rate.
• Nanonization: Produces nanoparticles (<1 µm) to improve solubility and bioavailability .
Technique: Micronization or nanonization
Materials:
• Milling agents (e.g., zirconia beads, stainless steel)
• Surfactants/stabilizers for nanosuspensions (e.g., Poloxamer, Tween 80
7. B) SOLID DISPERSION : Drug is dispersed in an inert carrier (e.g., PEG, PVP) in the solid state to
improve wettability and solubility. (Vemula VR et al., 2010).
Types of solubility enhancement on basis of carrier
14. HOT MELT EXTRUSION (For Ibuprofen) :
Hot Melt Extrusion (HME) is a thermal processing technique in which active pharmaceutical ingredients of
Ibuprofen are blended with thermoplastic polymers and other excipients. The mixture is heated above the
polymer's glass transition or melting point, allowing for mixing, melting, and shaping into a solid dosage form
of Ibuprofen .(Kadam SV et al., 2013)
Mechanism:
• Heat + Mechanical shear → Melting + Homogenization
• API of IBUPROFEN dispersed in polymer matrix → solid solution or dispersion
Common Polymers and Excipients Used for ibuprofen :
• Polymers: PVP, HPMC, Eudragit, Soluplus
• Plasticizers: PEG, triethyl citrate
• Stabilizers: Antioxidants, surfactants
15. METHOD / PROCESS STEPS : (Pinon et al., 2012)
🔹 Step 1: FEEDING
🔹 Step 2: MELTING
🔹 Step 3: MIXING & CONVEYING
🔹 Step 4: EXTRUSION THROUGH DIE
🔹 Step 5: COOLING
🔹 Step 6: CUTTING/ GRANULATION
18. ADVANTAGES of Hot Melt Extrusion :
• Solvent-free process
• Continuous manufacturing
• Enhances drug solubility.
• Improves bioavailability
• Provides controlled or sustained release
• Uniform drug distribution
• Compatible with a wide range of polymers
DISADVANTAGES of Hot Melt Extrusion :
• High processing temperatures
• Requires specialized equipment.
• Limited to thermally stable drugs and excipients.
• High energy consumption.
• Possible phase separation.
• Difficult to process high drug loads.
• Initial formulation development is complex.
• Cooling step required.
19. SOLVENT EVAPORATION METHOD :
• Mechanism:
1. API of ibuprofen and polymer are dissolved in a volatile organic solvent.
2. This solution of ibuprofen is emulsified into an aqueous phase (usually with
surfactant).
3. As the solvent evaporates, solid particles or films form, encapsulating the
ibuprofen tablet.
• Key Instruments Used in Solvent Evaporation :
20. METHOD / PROCESS STEPS :
(Singh A. K et al., 2015)
• Single Emulsion (O/W) Technique :
1. Preparation of Organic Phase:
2. Emulsification:
3. Solvent Evaporation:
4. Separation and Washing:
5. Drying:
• Double Emulsion (W/O/W) Technique :
1. Preparation of Organic Phase (O) :
2. Primary Emulsification (W/O):
3. Secondary Emulsification (W/O/W):
4. Solvent Evaporation:
5. Separation and Washing:
6. Drying:
21. Advantages of Solvent Evaporation Method:
(Okonogi S et all., 1997)
• Simple and widely used.
• Effective for encapsulating both hydrophilic and hydrophobic drugs.
• Enables formation of nanoparticles, microspheres, and solid dispersions.
• Good control over particle size.
• Facilitates high drug loading.
• Preserves drug stability.
• Applicable for sustained and controlled release formulations.
• Cost-effective.
Disadvantages of Solvent Evaporation Method:
• Use of organic solvents
• Residual solvent
• Requires complete solvent removal
• Low scalability
• Not suitable for heat-sensitive solvents or polymers.
• Time-consuming drying steps
• Emulsion instability
• Risk of drug degradation
22. C) Cryogenic Technology :
Utilizes low temperatures to process drugs, preserving their stability and
enhancing solubility. Techniques include cryomilling and cryoprecipitation.
D) Nanotechnology-Based Systems :
Incorporates nanoparticles, liposomes, micelles, and dendrimers to enhance
solubility and bioavailability. These systems offer controlled release and
targeted delivery.
23. CHEMICALAPPROACHES: (Prasad D, et all.2017)
A) Change of Ph :
Altering the pH can shift the ionization state of molecules, affecting
their solubility, reactivity, and stability. It's commonly used to enhance
drug absorption or alter reaction conditions.
B) Use of Buffer :
Buffers maintain a stable pH during chemical reactions or
formulations, ensuring optimal conditions for activity or
stability. They prevent degradation due to pH fluctuations.
24. C) Derivatization :
This involves chemically modifying a compound to
enhance properties like detectability, stability, or
solubility by adding functional group.
D) Complexation :
Complexation forms coordination complexes between a
molecule and metal ions or ligands, improving solubility
or stability.
E) Salt Formation :
Converting a compound into a salt improves its water
solubility, bioavailability, and stability. This is a common
approach in pharmaceutical formulation.
25. MICSELLENEOUS METHODS : (Saritha AS et all., 2015)
A) Supercritical Fluid Technology :
Utilizes supercritical fluids (like CO ) to dissolve or process
₂
drugs, allowing precise control over particle size and formula-
tion.
B) Micellar Solubilization :
Incorporates surfactant micelles to solubilize hydrophobic
drugs, enhancing their solubility and bioavailability.
C) Self-Emulsifying Drug Delivery Systems (SEDDS) :
Formulations that spontaneously form emulsions upon contact
with gastrointestinal fluids, enhancing drug solubility.
26. D) Direct Capsule Filling :
Involves filling capsules directly with drug powders or
granules, simplifying formulation and enhancing solubility.
This method is particularly useful for poorly soluble drugs.
E) Electrospinning :
Uses an electric field to produce nanofibers from polymer
solutions, which can encapsulate drugs and enhance solubility.
This technique offers controlled release properties.
27. CONCLUSION
Therapeutic activity of a drug depends on its bioavailability and solubility. Solid dispersion is crucial for
increasing solubility, dissolution, and bioavailability (Thorat YS et all., 2011). Oral dispersible tablets offer
immediate conversion of solid to liquid after administration, providing market opportunities for a wide
range of drugs. Rapid disintegrating dosage forms have been commercialized and are expected to
become more popular due to increased patient demand (Saritha AS et all., 2015). Future improvements
include large-scale manufacturing, better predictions of drug/carrier combinations, and physical stability
during processing and storage.
28. REFERENCE
1. Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. International journal of pharmaceutical sciences review
and research. 2010 ;5(1):41-51.
2. Thorat YS, Gonjari ID, Hosmani AH. Solubility enhancement techniques: a review on conventional and novel approaches.
International journal of pharmaceutical sciences and research. 2011 1;2(10):2501.
3. Jagtap S, Magdum C, Jadge D, Jagtap R. Solubility enhancement technique: a review. Journal of pharmaceutical sciences and
Research. 2018 1;10(9):2205-11.
4. Kumar S, Singh P. Various techniques for solubility enhancement: An overview. The Pharma Innovation. 2016;5(1, Part A):23.
5. Kadam SV, Shinkar DM, Saudagar RB. Review on solubility enhancement techniques. IJPBS. 2013 ;3(3):462-75.
6. Pinon-Segundo, E., Nava-Arzaluz, M. G., & Lechuga-Ballesteros, D. (2012). Pharmaceutical Polymeric Nanoparticles Prepared by
the Double Emulsion-Solvent Evaporation Technique. Recent Patents on Drug Delivery & Formulation, 6(3), 252–266.
7. Giri, T. K., Choudhary, C., Ajazuddin, A., & Tripathi, D. K.(2013) Double Emulsions (W/O/W Emulsions): Encapsulation of Plant
Bioactives. Food Research International, 51(1), 1–18.
8. Novriadi, D, Sato, Y, & Yoshida, H. (2016) Fabrication of Fucoxanthin-Loaded Microsphere (F-LM) by Two Steps Double-
Emulsion Solvent Evaporation Method and Characterization of Fucoxanthin Before and After Microencapsulation.
9. Singh, A. K., Kumar, M., & Upadhyay, P. K. (2015) Methods for the Encapsulation of Hydrophilic Drugs in Lipid-Based
Nanocarriers, Solid Lipid Nanoparticles, and Nanostructured Lipid Carriers: A Short Review and Perspective.
10. Behera, B. C., Sahoo, S. K., Dhal, S., Barik, B. B., & Gupta, B. K. (2008).Characterization of Glipizide-Loaded Polymethacrylate
Microspheres Prepared by an Emulsion-Solvent Evaporation Method.
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REFERENCE
