Contents

Cover

Title page

Copyright page

Preface

Section I: Preliminary Considerations and Selection of Raw Materials

Chapter 1: Pre-formulation Design and Considerations
1. Introduction
2. Project Goals and Formulation Design
3. Selecting The Right Ingredients for Your Design
4. Pre-formulation Considerations—Vehicle Examples
5. Choosing a Surfactant
6. Selecting a Suitable Emulsifier
7. Other Pre-formulation Considerations
8. Botanicals
9. Choice of Preservation Systems
10. Manufacturing Considerations
11. Reading a Technical Product Sheet
12. Regulatory Considerations
13. Safety of the Formulation
14. Summary
Chapter 2: The Use of Thickeners in Topically Applied Formulations
1. Introduction
2. Rheology
3. Classifying Thickeners
4. Advantages and Disadvantages of Natural Thickeners
5. Inorganic Thickeners
6. Formulating With Thickeners
7. Further Example Formulations
8. Summary
Chapter 3: The Incorporation of Delivery Systems into Topical Formulations: A Case Study on the Use of Salicylic Acid for Acne Treatment
1. Abstract
2. Background
3. Motivation For Encapsulaton Of Salicylic Acid
4. Formulations With Sa And Encapsulation Technologies
5. Summary/Conclusion And Future Perspectives
Chapter 4: Formulating Skin Care Products with Silicones: Approaches and Strategies
1. Introduction to Silicones
2. Major Categories of Silicones and Their Properties
3. Silicone Applications and Benefits in Personal Care Formulations
4. Moisturizers (Hand and Body Lotions)
5. Facial Care (Anti-aging Products)
6. Color Cosmetics
7. Sun Protection
8. Shampoos
9. Hair Conditioners
10. Skin Cleansers and Body Washes
11. Antiperspirants and Deodorants
12. Formulation Considerations
13. Formulary
14. CATEGORY: Moisturizers
15. CATEGORY: Face Care Formulations
16. CATEGORY: Color Cosmetics
17. CATEGORY: Sunscreens
18. CATEGORY: Antiperspirants
19. CATEGORY: Cleansers and Shampoos
20. CATEGORY: Hair Conditioners
21. Summary
Chapter 5: The Use of Corn-derived Ingredients in Personal Care Applications
1. Introduction
2. Zea Mays (Corn) Starch
3. Modified Starches
4. Hydrolyzed Corn Starches
5. Additional Applications for Corn-derived Ingredients in Topical Formulations
6. Summary

Section II: Formulation, Processing and Production Techniques

Chapter 6: Emulsions and their Characterization by Texture Profile Analysis
1. Introduction
2. Basic Principles of Emulsion Technology
3. Phenomena Involved in Emulsion Instability
4. Mechanisms of Emulsion Stabilization by Emulsifiers
5. Measurement of Emulsion Stability
6. Definitions of Key Phenomena in Emulsion Technology
7. Sensorial and Textural Properties of Emulsions
8. Texture Profile Analysis (TPA)
9. Determination of Textural Attributes from Texture Profile Analysis
10. Analysis of Commercial Lotions and Creams by Texture Profile Analysis
11. Analysis of O/W Emulsions by Texture Profile Analysis
12. Concluding Remarks
13. Acknowledgements
Chapter 7: High Internal Phase Water-in-oil Emulsions
1. Introduction
2. High Internal Phase Water-in-oil Emulsions (HIPEs)
3. Stabilization in HIPEs
4. Topical Delivery Systems Based Upon HIPEs
5. Future Prospects for HIPEs
6. Summary
Chapter 8: Manufacturing Topical Formulations: Scale-up from Lab to Pilot Production
1. Introduction
2. Overview of Key Scale-up Considerations
3. Process Design
4. Scale-up Principles
5. Quality by Design Principles
6. Anchor Speed
7. Disperser Speed
8. Mixing Time
9. Mix Temperature
10. Vacuum Pressure
11. Transfer Pressure
12. Experimental Design
13. Process Equipment: Pilot Scale
14. Formulation Specific Requirements
15. Filling & In-process Analytical Equipment
16. Facilities and Engineering Issues
17. Raw Material Considerations
18. Summary
Chapter 9: Foam: A Unique Delivery Vehicle for Topically Applied Formulations
1. Introduction
2. Overview of the Market: Current Foam Technologies
3. The Rosetta Stone Of Foam
4. Water-containing Foams
5. Nanoemulsion Foam
6. Hydroethanolic Foam
7. Potent Solvent Foam
8. Water-free Foams
9. How to Formulate Foam Products
10. Methods of Evaluation of Foam Products
11. Summary

Section III: Testing and Measurements Methods

Chapter 10: Using Experimental Design to Optimize Formulations
1. Introduction
2. What is Experimental Design?
3. Factorial Designs
4. Mixture Designs
5. Mixture/Amount Design
6. Exactly What Is Synergy?
7. The Cornell Approach
8. How To Get Started
9. Example
10. JMP Leverage Plots
11. Additional Thoughts
12. Conclusions
Chapter 11: Rheological Properties of Topical Formulations
1. Introduction
2. Rheological Measurements
3. Instrumentation
4. Rheological Additives
5. Formulation of Topical Products
6. Summary
Chapter 12: Viscosity Measurement for Topically Applied Formulations
1. Introduction
2. Definitions and Units of Viscosity
3. Importance of Shear Rate
4. The Stages in Product Development for the Consideration of Viscosity Evaluation
5. Instrumentation for Measurement
6. Reading and Understanding Viscosity Specifications
7. Measurement Key Considerations
8. Summary
Chapter 13: Fourier Transform Infrared (FTIR) Spectroscopic Imaging Analysis of Topical Formulations
1. Introduction
2. Experimental Methods
3. Imaging Formulations: Examples
4. Summary

Section IV: Sensory and Elegancy

Chapter 14: Creating Appealing Topically Applied Formulations: Linking Physical Aspects to Marketing Psychology
1. Introduction
2. Luxury Goods Business
3. Consumer Perception—Multiple Factors At Play
4. Matching the Product to the Consumer
5. Sustained Success
6. Research That Changed Everything
7. The Challenge of Matching Sensorial Attributes
8. Selecting Ingredients for a Novel Approach
9. Real Security
10. Combining Elements of Development
11. Involving Scale-up and Manufacturing
12. Time Scale
13. Summary
Chapter 15: The Use of Fragrance in Topically Applied Formulations
1. Introduction
2. Aroma Chemicals
3. Natural Products
4. Terpenes: Where Nature and Chemistry Collide
5. Natural and Organic Fragrances
6. Hydroalcoholics
7. The Importance of Weak Forces
8. Emulsion Systems
9. Surfactant Systems
10. Controlled Release
11. Malodor
12. Regulatory Essentials
13. Aromascience
14. Summary

Section V: Stability and Preservation

Chapter 16: Stability Testing for Topical Formulation Development
1. Introduction
2. Types of Topically Applied Products
3. Product Instability
4. Considerations
5. Chemical Stability Measurements
6. Physical Stability Measurements
7. Summary
Chapter 17: Preservation of Topical Formulations: An Historical and Practical Overview
1. Historical Perspective on Microbiology and Preservation in Personal Products
2. Preservative Types and Their Usage in Personal Care Products
3. Isothiazolinones
4. Halogenated Preservatives
5. Other Preservatives
6. Non-classified Preservatives (non-regulated)
7. Final Words
Chapter 18: Microbiological Stability for Skin Care Formulations
1. Introduction
2. Preservation Of Topical Formulations – Defining The Purpose
3. Types And Classes Of Preservatives
4. Formulation Design And Preservation
5. Preservative Blends
6. Natural Preservatives
7. Preservative Efficacy Testing
8. Ensuring Preservative Stability
9. Regulatory And Safety Aspects Of Preservative Use In Cosmetics
10. Summary

Section VI: Color Cosmetics

Chapter 19: Lip Care Product Formulation Strategies
1. Types of Lip Products
2. Setting Specifications and Path of Development
3. Ingredients
4. Pigment Dispersants/Emulsifiers
5. Common Formulation Challenges
6. Physical Stability Requirements
7. Processing
8. Packaging
9. Summary and the Future Perspective of Lip Care Formulations
Chapter 20: Formulation of Nail Care Products
1. Introduction
2. Nail Lacquer Chemistry and Formulation
3. Nail Lacquer Testing
4. Nail Lacquer Manufacture and Quality Control
5. Nail Lacquer Packages
6. Non-lacquer Nail Products
7. Summary

Section VII: Sunscreens

Chapter 21: Formulation of Sunscreens in the United States
1. Introduction
2. SPF and UVA Protection in Sunscreen
3. Determination of SPF
4. High SPF
5. UVA Protection
6. Broad Spectrum Protection and Prevention of Skin Damage
7. Ingredients and Formulation Strategies
8. Product Forms
9. Key Formulation Considerations
10. New Active Ingredients on the Horizon
11. Summary
Chapter 22: Formulating a Day Cream with SPF: A Case Study
1. Introduction
2. Background
3. UV Damage
4. Sunscreens: An Overview
5. Formulation Considerations
6. Summary: Our Final Formulation

Glossary of Terms, by Chapter

Author Biographies

Index

End User License Agreement

List of Tables

Chapter 1

Table 1. Cosmetic Ingredient Reference Sources

Chapter 4

Table 1. Silicone Types and Benefits by Category
Table 2. Silicone Benefits, as Arranged by “Family”
Table 3. Benefits of Silicones for Sun Care Development, as Arranged by “Family”

Chapter 6

Table 1. A typical o/w emulsion composition.
Table 2. Selected commercial products subjected to Texture Profile Analysis. Viscosity data, courtesy of Timothy Gillece, were obtained with an Ares G2 strain controlled rheometer utilizing parallel plates geometry.
Table 3. Selected textural attributes of several commercial creams and lotions.
Table 4. Composition of four selected cream base emulsions subjected to Texture Profile Analysis.

Chapter 8

Table 1. Summary of Mixing Scale-up Principles
Table 2. Example Target Product Profile: Topical Pain Treatment Gel in Metered-Dose Pump
Table 3. Topical Pain Treatment Gel in Metered-Dose Pump: Example Quality Target Product Profile vs. Critical Quality Attributes
Table 4. Topical Pain Gel in Metered-Dose Pump: Process Map
Table 5. Topical Pain Treatment Gel in Metered-Dose Pump: Risk Assessment, Focus Area 2: Mixing / Vacuum
Table 6. Risk Prioritization Numbering System: Severity
Table 7. Risk Prioritization Numbering System: Occurrence
Table 8. Risk Prioritization Numbering System: Detection
Table 9. Topical Pain Gel in Metered-Dose Pump: Example FMECA Exercise, Focus Area 1: Selected Raw Material Attributes
Table 10. Topical Pain Gel in Metered-Dose Pump: Example FMECA Exercise, Focus Area 2, Mixing Process Parameters
Table 11. Topical Pain Gel in Metered-Dose Pump: Example FMECA Exercise, Focus Area 3, Filling Process Parameters
Table 12. Topical Pain Treatment Gel in Metered-Dose Pump: Example Designed Experiment
Table 13. Topical Pain Treatment Gel in Metered-Dose Pump: Designed Experiment – Full Factorial Experimental Plan (Randomized)
Table 14. Topical Pain Treatment Gel in Metered-Dose Pump: Designed Experiment – Full Factorial Experimental Plan (Randomized) Modeling Results, Effects Testing
Table 15. Selected Impeller Characteristics

Chapter 9

Table 1. Classification of foam technology platforms, corresponding to traditional topical dosage form designations
Table 2. Examples of Cosmetic and Nonprescription Emollient Foams.
Table 3. Minocycline Foam 1% and 4%; Measure Skin Delivery Comparison
Table 4. Minocycline Foam 1% and 4%: Success rate at Day 3, Day 7 (End of Treatment) and Day 14 (Follow-up)

Chapter 10

Table 1. the experimental batches and results
Table 2. Scheffé Coefficients
Table 3. ANOVA Table
Table 4. Summary of Fit

Chapter 11

Table 1. Units of rheological properties
Table 2. Typical shear stress and shear rate ranges
Table 3. Flow models
Table 4. Rheological Properties of Skin Creams

Chapter 12

Table 1. Specification properties for Polyisobutene (trade name: Permethyl 106A)

Chapter 15

Table 1. HSP of some common aroma chemicals and cosmetic ingredients
Table 2. IFRA Categories for Fragrance Use
Table 3. EU Allergens

Chapter 17

Table 1. Organic Acid comparison: pKa, pH, and use levels

Chapter 18

Table 1. Examples of formulation factors and related general consideration
Table 2. Key Examples of Interaction of Preservatives with Other Formulation Ingredients
Table 3. Examples of Adsorbents with Susceptible Preservatives
Table 4. Conditions Affecting the Performance of a Preservative and Recommendations for Improvement
Table 5. Examples of Commercially Available Preservative Blends

Chapter 19

Table 1. Melting point ranges for a variety of waxes
Table 2. Lipstick with Polyethylene
Table 3. Long-wearing Lipstick with Polyisobutene
Table 4. Longwearing lip gloss with alkyl silicone resin
Table 5. Lip Gloss

Chapter 20

Table 1. Nail Lacquer Test Methods & Equipment

Chapter 21

Table 1. FDA approved UV filters.^1,2 *Ecamsule is used only under NDA.
Table 2. New UV filters currently under TEA evaluation with the FDA1

Chapter 22

Table 1. Comparison between physical blocks, physical filters, and chemical filters.
Table 2. Zinc oxide and Titanium oxide status as sunscreens
Table 3. Overview of chemical filters authorized to use in Europe and/or in the United States and/or in Japan.
Table 4. Overview of the advantages and limitations of key chemical filters.^10-12
Table 5. Overview of the advantages and limitations of galenic forms.
Table 6. Example of facial moisturizers with SPF.

List of Illustrations

Chapter 2

Figure 1. Rheological Fluid Flow Showing Sheer Rate
Figure 2. Newtonian Fluid behavior
Figure 3. Pseudoplastic Fluid behavior
Figure 4. Dilatent Fluid behavior
Figure 5. Thixotropic Fluid behavior
Figure 6. Chemical Structure of Cellulose
Figure 7.
Figure 8. Chemical Structure of Xanthan Gum
Figure 9. Chemical Structure of Alginate
Figure 10. Cross-linking in Polyacrylic Thickeners
Figure 11. Associative Thickeners

Chapter 3

Figure 1. Structure of sub-micron spheres.
Figure 2. Sub-micron technology as (A) raw material and (B) in a facial cleanser at 2% SA.
Figure 3. Skin pH after treatment with sub-micron technology comprising of SA.
Figure 4. Longevity of SA from sub-micron technology vs. free over a six-hour period.
Figure 5. Skin Extractions for validation of controlled release of SA.
Figure 6. Enhanced deposition of SA after treatment with 2 % SA from free vs. sub-micron technology from a body wash.

Chapter 4

Figure 1. Dimethicone
Figure 2. Dimethiconol
Figure 3. Cyclopentasiloxane
Figure 4. Amodimethicone (where R is –OH or –CH3)
Figure 5. PEG-12 Dimethicone
Figure 6. Phenyl Trimethicone
Figure 7. Cetyl Dimethicone
Figure 8. Water Permeability for Alkyl-Modified Silicones versus other selected materials
Figure 9. Trimethylsiloxysilicate
Figure 10. Wrinkle-masking Effect of Silicone Elastomer Powder
Figure 11. Sebum Control with Silicone Elastomer Powder; *indicates significant difference at the 99% confidence level

Chapter 6

Figure 1. Illustration of a dispersed oil droplet in a typical o/w emulsion stabilized with an emulsifier.
Figure 2. Illustration of a dispersed water droplet in a typical w/o emulsion stabilized with an emulsifier.
Figure 3. Example of a Pickering emulsion, a type of o/w emulsion, stabilized with solid particles at the interface of the oil and water phase.
Figure 4. Stability image diagrams corresponding to morphological changes of emulsions.
Figure 5. Zeta potential diagram of a negatively charged emulsion droplet.
Figure 6. Image of a Texture Analyzer
Figure 7. Probes utilized to conduct Texture Profile Analysis: (a) TA-11; (b) TA-10; (c) TA-10ss; (d) TA-23; and (e) TA-18.
Figure 8. Example of a typical Texture Profile Analysis curve denoting specific length, peak height, and area measurements used to calculate textural attributes.
Figure 9. Chart of firmness for emulsion systems based on (A) carbomer, (B) acrylic acid/VP crosspolymer, (C) PVM/MA decadiene crosspolymer, and (D) sodium polyacrylate.
Figure 10. Chart of compressibility for emulsion systems based on (A) carbomer, (B) acrylic acid/VP crosspolymer, (C) PVM/MA decadiene crosspolymer, and (D) sodium polyacrylate.
Figure 11. Chart of resilience for emulsion systems based on (A) carbomer, (B) acrylic acid/VP crosspolymer, (C) PVM/MA decadiene crosspolymer, and (D) sodium polyacrylate.

Chapter 8

Figure 1. shows the general shape of a mixer power curve, on log-log coordinates.
Figure 2. Mixer Schematic
Figure 3. Pilot Plant Scale-up and Quality by Design
Figure 4. Topical Pain Gel in Metered-Dose Pump: Process Flow Chart with Focus Areas
Table 7. Risk Prioritization Numbering System: Occurrence
Figure 5. Contour Plot: Mixing Time and Anchor Speed Effect on Viscosity
Figure 6. Contour Plot: Mixing Time and Disperser Speed Effect on Viscosity
Figure 7. Multi-Shaft Mixer: 1.5 Gal Unit
Figure 8. Multi-Shaft Mixer: 15 Gal Unit
Figure 9. Multi-Shaft Mixer: 35 Gal Unit
Figure 10. An Anchor-Disperser Impeller Combination
Figure 11. Anchor-Disperser-Augur Impeller Combination
Figure 12. High-Speed Disperser Blade
Figure 13. Rotor-Stator Homogenizer
Figure 14. A Single-Station Filling Machine
Figure 15. A Typical Tube Filling Machine
Figure 16. NIR Spectrum for Mixing of a Gel

Chapter 9

Figure 1. Betamethasone Emollient Foam—clinical improvement of psoriasis lesions following three weeks of treatment
Figure 2. Usability preference–Foam vs. Cream
Figure 3. Metronidazole 1% emollient foam versus commerical cream.
Figure 4. The skin penetration profile of Metronidazole 1% emollient foam with 2.5% propylene glycol as a penetration enhancer (MZPG) and without propylene glycol (MZ) vs. cream.
Figure 5. Percent reduction of inflammatory, non-inflammatory and total count of acne lesions
Figure 6. Photographic documentation of the effect of Minocycline foam in a severe acne patient. Dramatic improvement is observed after 9 weeks of treatment
Figure 7. Photographic documentation of the effect of Minocycline foam in pediatric patients with impetigo, demonstrating visible improvement or clearance of lesions within 3 to 7 days of treatment.
Figure 8. Breakable emollient foam (Foamix) vs. quick breaking hydroethanolic foam

Chapter 10

Figure 1. Comparison schematic: Mixture Design vs. Factorial Design
Figure 2. Calculating the miles per gallon Gasolines A and B
Figure 3. The Cornell Additive Blending Plot of Gasolines A and B
Figure 4. Diagram of multi-ingredient design concerns. Each end of the linear design space for a binary blend represents 100% of one ingredient and 0% of the other. Each apex of the equilateral triangle (three ingredients) or pyramid (four ingredients) represents 100% of the ingredient indicated while the side of the triangle (or pyramid) directly opposite represents that same specific ingredient at 0%.
Figure 5. Mixture Design Types under discussion
Figure 6. Batch display in actual design space
Figure 7. 2-D Data Plot
Figure 8. 3-D Data Plot
Figure 8. Comparison of Significance Shown in Leverage Plots
Figure 10. Plot of Residuals

Chapter 11

Figure 1. Applying force to an area
Figure 2. Shear stress as a function of shear strain
Figure 3. Basic model for flow under an external force
Figure 4. Shear stress as a function of shear rate for Newtonian fluids
Figure 5. Viscosity as a function of shear rate for Newtonian fluids
Figure 6. Viscosity as a function of shear rate for Non-Newtonian fluids (shear thinning)
Figure 7. Viscosity as a function of shear rate for Non-Newtonian fluids (shear thickening)
Figure 8. Flow profiles of Newtonian and Non-Newtonian systems: Shear stress as a function of shear rate
Figure 9. Flow profiles of Newtonian and Non-Newtonian systems: Viscosity as a function of shear rate
Figure 10. Flow profiles of two products formulated to the same viscosity
Figure 11. Calculating yield value by interpolation to shear rate = 0
Figure 12. Recovery after application
Figure 13. Thixotropy loop
Figure 14. Arrhenius plot: Viscosity as a function of 1/T
Figure 15. Viscoelastic models: (a) Maxwell model (b) Kelvin/Voigt model
Figure 16. Creep/Recovery test (constant stress)
Figure 17. Oscillatory elastic and viscous behavior
Figure 18. Strain Sweep: Modulus as a function of strain
Figure 19. Frequency sweep: Modulus as a function of frequency
Figure 20. Zahn and Ford Cups (courtesy of Byk-Gardner)
Figure 21. Ostwald capillary viscometer
Figure 22. Cannon-Fenske and Ubbelohde capillary viscometers (courtesy of Cannon Instrument Company)
Figure 23. Differences between controlled stress and controlled rate rheometers
Figure 24. A schematic structure of a controlled stress rheometer
Figure 25. The DV II + Pro Viscometer (courtesy of Brookfield Engineering Laboratories)
Figure 26. A schematic presentation of the concentric cylinder geometry
Figure 27. A schematic presentation of a cone and plate geometry
Figure 28. (a) The Nova Rheometer (courtesy of ATS Rheosystems); (b) The Kinexus Rheometer (courtesy of Malvern Instruments); (c) The MCR Rheometer (courtesy of Anton-Paar); (d) The MARS Rheometer (photograph used by permission from Thermo Fisher Scientific); (e) The Discovery Hybrid Rheometer (courtesy of TA Instruments)
Figure 29. (a) A capillary breakup extensional rheometer and (b) a rheometer/microscope combination (photograph used by permission from Thermo Fisher Scientific)
Figure 30. Schematic representation of the gelling mechanism of carrageenan (courtesy of FMC Corporation)
Figure 31. A representative chemical structure of xanthan gum (graph reproduced by permission of CP Kelco U.S., Inc. and affiliated companies; members of the J.M. Huber family of companies; © 2008 CP Kelco U.S., Inc., and its affiliates)
Figure 32. Effect of heating/cooling and shearing on the conformation of xanthan gum (graph reproduced by permission of CP Kelco U.S., Inc. and affiliated companies; members of the J.M. Huber family of companies; © 1988 CP Kelco U.S., Inc., and its affilates)
Figure 33. Synergistic effect of blends of xanthan gum and guar gum (graph reproduced by permission of CP Kelco U.S., Inc. and affiliated companies; members of the J.M. Huber family of companies; © 2008 CP Kelco U.S., Inc., and its affiliates)
Figure 34. Flow profiles of various rheological additives in water at 0.5% concentration (graph reproduced by permission of CP Kelco U.S., Inc. and affiliated companies; members of the J.M. Huber family of companies; © 2008 CP Kelco U.S., Inc., and its affiliates)
Figure 35. Chemical structure of an acrylic copolymer.
Figure 36. Schematic presentation of the neutralization of an alkali swellable polymer chain (a) coiled (b) uncoiled
Figure 37. Change in viscosity of an alkali swellable polymer in water as a function of pH
Figure 38. Schematic presentation of micelle formation
Figure 39. A schematic model of hydrophobically modified cellulose ether (HMCE) (reprinted with permission of Ashland Inc.; © 2013 Ashland Inc.)
Figure 40. Viscosity as a function of shear rate in systems containing HMHEC and HEC (reprinted with permission of Ashland Inc.; © 2013 Ashland Inc.)
Figure 41. Viscosity of HMASP thickeners as a function of pH⁶¹
Figure 42. The effect of the size of the hydrophobic group of a HMASP on viscosity as a function of shear stress⁵⁶
Figure 43. Effect of hydrophobic modification on the viscosity of HMUP in water (reprinted with permission from Reference 62. Copyright (1991) American Chemical Society)
Figure 44. The effect of concentration on the viscosity of two HMUP rheological additives in water (reprinted with permission from Reference 62. Copyright (1991) American Chemical Society)
Figure 45. Effect of surfactant concentration on hydrophobically modified urethane polymers (HMUP) (•) 2% Associative Thickener (AT)18-19 HMUP with octadecyl end groups; (o) 2.5% AT15-19 with pentadecyl end groups; (□) 5% AT17:1-19 with 9- heptadecenyl end groups⁶³
Figure 46. The effect of molecular weight and hydrophobic groups on low shear limiting viscosity of hydrophobically modified ether polymers (HMEP) (reprinted with permission from Reference 64. Copyright (1991) American Chemical Society)
Figure 47. Mineral structure of montmorillonite clay (courtesy of US Geological Survey⁶⁶)
Figure 48. Possible arrangements of clay platelets: (a) edge-to-edge, (b) edge-to-face, (c) face-to-face, from Reference 68, reproduced with kind permission of The Clay Minerals Society, publisher of Clays and Clay Minerals
Figure 49. Viscosity as a function of concentration for bentonite and hectorite solutions (© 2008 Elementis Specialties, Inc.; reprinted with permission of Elementis Specialties, Inc.^69a)
Figure 50. Schematic presentation of a reaction between a quaternary ammonium chloride and a silicate mineral
Figure 51. Effect of polar activation on the viscosity of organoclays (courtesy Elementis Specialties; © 2008 Elementis Specialties, Inc.; reprinted with permission of Elementis Specialties, Inc.^69b)
Figure 52. Flow profiles of skin creams: Viscosity as a function of shear rate
Figure 53. Flow profiles of skin creams: Viscosity as a function of shear stress
Figure 54. Skin creams: Thixotropic loop (shear stress as a function of shear rate: “up” and “down” curves)
Figure 55. Skin creams: Calculating yield values
Figure 56. Skin creams: Demonstration of Creep/Recovery
Figure 57. Skin creams: Strain sweep
Figure 58. Combination of two rheological additives to achieve an “ideal” target flow profile

Chapter 12

Figure 1. Schematic illustration of a model of fluid between two plates
Figure 2. Dependence of viscosity on shear rate, for different fluid types
Figure 3. Flow profile for a shear thinning (non-Newtonian) fluid with a Newtonian plateau
Figure 4. Flow profile of two fluids with different dependence of viscosity on shear rate
Figure 5. Flow curves showing fluids without (A) and with thixotropy (B)
Figure 6. The viscosity as a function of pH, at different levels of salt content provided for a commercially available rheology modifier (reprinted by permission from Presperse Corporation)
Figure 7. Viscosity and pH results for a model cleansing system monitored over 4 weeks of stability testing (reprinted by permission from Presperse Corporation)
Figure 8. Brookfield DV-III Ultra viscometer (reprinted by permission from Brookfield Engineering)
Figure 9. Spindles used for Brookfield viscosity measurement (reprinted by permission from Brookfield Engineering)
Figure 10. T-bar spindles for use with a helipath attachment (reprinted by permission from Brookfield Engineering)
Figure 11. Example of flow curves for two commercial lotions, scaled linearly (top) and logarithmically (bottom)

Chapter 13

Figure 1. Schematic of a Fourier transform infrared (FTIR) imaging microspectrometer measurement. Complete IR spectra are collected at each pixel providing spatially resolved IR spectroscopic characterization of the sample area imaged.
Figure 2. Spectroscopic images of a commercial sunscreen formulation at 2 different spatial resolution (25 × 25 μm/pixel) and (6.25 × 6.25 μm/pixel). The images show the distribution and intensity of a two chemical components in the formulation. The image of the 1,670 cm^-1 peak is specific to the base formulation while the peak imaged at 1,030 cm-1 is specific to octocrylene, one of the UV actives in this formulation. The right-hand image in both rows shows the relative intensity of the octocrylene peak to the formulation peak thereby removing intensity variations associated with film thickness variations.
Figure 3. FTIR images of a commercial topical insect repellant formulation. The images show the distribution and relative concentration of N,N-Diethyl-meta-toluamide within the formulation. The spectral assignments are based on molecular FTIR spectra of the formulation and pure N,N-Diethyl-meta-toluamide, as shown in the figure.
Figure 4. FTIR images showing the changing concentration of DEET within the formulation film over a period of several hours at room temperature. These images directly represent the spatial distribution and concentration changes of DEET within the formulation film.
Figure 5. FTIR images showing the changing concentration (slow release) of medicinal alcohols from a petrolatum-based formulation. These images are generated from the ratio of the peak corresponding to the volatile active normalized to a peak from the non-volatile petrolatum base. Thus the images capture directly the changing distribution and concentration of specific chemical components within the formulation film.
Figure 6. FTIR images showing the distribution of salicylic acid in a topical analgesic formulation generated by imaging an acid peak specific to the active. In this case the active peak intensity is not normalized to a component of the formulation base. The image is to illustrate the non-uniform distribution of the active and the apparent localization of crystals in the formulation film.

Chapter 14

Figure 1. Fragrance dominates sensation
Figure 2. Optimum product development flow chart

Chapter 15

Figure 1. Fragrance triangle
Figure 2. Example output
Figure 3. The vanillin structure
Figure 4. Steam distillation process
Figure 5. Terpene structures
Figure 6. Hydroalcoholic compositions
Figure 7. Hanson space
Figure 8. Substrate effect on aroma chemical headspace (5 ex.)⁸
Figure 9. Fragrance effects on micelles
Figure 10. Benzaldehyde + UV
Figure 11. Neutroleum type fragrance
Figure 12. Veilex
Figure 13. Zinc Ricinoleate
Figure 14. Cyclodestrin

Chapter 16

Figure 1. Emulsion structure
Figure 2. Emulsion (a) creaming and (b) sedimentation
Figure 3. Emulsion flocculation
Figure 4. Emulsion coalescence
Figure 5. Lamellar bilayer structure
Figure 6. A graph of a Zero Order Reaction with an initial concentration of 100% and reaction rate constant of 0.2%/day.
Figure 7. A linear graph of a First Order Reaction with an initial concentration of 100% and reaction rate constant of 0.1% Day¹.
Figure 8. A semi-log graph of a First Order Reaction with an initial concentration of 100% and reaction rate constant of 0.1% Day¹.
Figure 9. A semi-log graph the Arrhenius Relationship of First Order Reaction Rates and Reciprocal Absolute Temperature. E_A was selected as 1.5 kcal with a value of A of 2.1x10⁸ Day¹ which provides a reaction rate constant of 0.1% Day¹ at 20°C.

Chapter 17

Figure 1. Side-by-side comparison of the structures of benzoic acide and a common paraben

Chapter 18

Figure 1. Cosmetic Regulations and Preservation – US Food, Drug & Cosmetic (FD&C) Act
Figure 2. Topically Applied Formulations and Potential Sources of Contamination
Figure 3.
Figure 4. Conventional Cosmetic Preservatives
Figure 5. Percent of Beauty Launches since Jan 2008 with Preservatives
Figure 6. Percent of beauty launches since Jan 2008 – August 2012
Figure 7. Conditions Affecting the Availability and Efficacy of Preservatives ⁽²³⁾
Figure 8. Example Flow Diagram of Preservative Efficacy Test

Chapter 19

Figure 1. Melted lipstick being poured into metal split mold
Figure 2. Different lipstick shapes and designs
Figure 3. Illustration of D&C Red No.7 Ca.Lake and FD&C Blue No.1 Al. Lake
Figure 4. Fineness of Grind Gage (top left), along with dispersed titanium dioxide pigment grind (top right) and undispersed titanium dioxide pigment grind with streaks (bottom left).
Figure 5. Inner cup of lipstick package with splines

Chapter 20

Figure 1. Chemical structure of Nitrocellulose repeat unit in a polymer
Figure 2. Chemical structure of cellulose repeating unit in a polymer
Figure 3a. Chemical structure of acrylic acid monomer
Figure 3b. Chemical structure of methacrylic acid monomer
Figure 3c. Chemical structure of methyl methacrylate monomer
Figure 4. Chemical structures of formaldehyde (a) and toluenesulfonamide (b)
Figure 5. Chemical structure of styrene monomer
Figure 6. Reaction of isocyanate (a) and alcohol (b) to form a polyurethane (c)
Figure 7. Chemical structure of vinyl butyral monomer
Figure 8. Chemical structure of castor oil (triricinolein)
Figure 9. Chemical structure of camphor
Figure 10. Chemical structure of dibutyl phthalate (DBP)
Figure 11. Chemical structures of o-xylene, m-xylene and p-xylene (a, b, c)
Figure 12. Chemical structure of toluene
Figure 13. Chemical structure of n-heptane
Figure 14. Chemical structure of an ester
Figure 15. Chemical structures of ethyl acetate, n-propyl acetate and n-butyl acetate
Figure 16. Chemical structure of primary amyl acetate
Figure 17. Chemical structure of ethyl lactate
Figure 18. Chemical structures of four isomers of butyl acetate
Figure 19. Chemical structure of methoxypropanol (propylene glycol monomethyl ether)
Figure 20. Chemical structure of acetone
Figure 21. Chemical structure of D&C Red #6 dye
Figure 22. Chemical structure of FD&C Blue #1 dye
Figure 23. Chemical structure of carmine
Figure 24. Refraction of white light by a prism
Figure 25. Chemical structure of propylene glycol
Figure 26. Chemical structure of methoxypropanol (propylene glycol monomethyl ether)
Figure 27a. Digital Drying Time Recorder
Figure 27b. Cross Hatch Test Kit
Figure 27c. Digital Sward Hardness Rocker
Figure 27d. Pendulum Film
Figure 27e. Brookfield LVF Viscometer Photo courtesy of Brookfield Engineering
Figure 28. Nail Lacquer Pigment Suspension Defects
Figure 29. Process map for nail lacquer manufacturing

Chapter 21

Figure 1. Solar UV spectrum ranges; UVB = 290–320 nm; UVA ll (short UVA) = 320–340 nm; UVA l (long UVA) = 340–400 nm
Figure 2. A typical in vitro absorbance vs. wavelength curve for TiO2. The critical wavelength (λcrit) is the dividing point of the area under the absorbance curve (90% : 10%)
Figure 3. Degree of UVB/UVA penetration into the layers of the skin: UVB: mainly penetrates and interacts with epidermal components; UVA: penetrates deeper, reaching the dermis where the structural components (elastin and collagen) as well as blood vessels reside.
Figure 4. Organic Sunscreens: Chromophores absorb UV radiation
Figure 5. Inorganic Sunscreens: Particles reflect, scatter, and increase the path-length of UV radiation (A) and absorb UV radiation (B)

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Library of Congress Cataloging-in-Publication Data:

ISBN 978-1-119-36362-0

Preface

Originally published by Allured in 2013 with the title “Apply Topically”, this reissued book has the new title of “Handbook of Formulating Dermal Applications” and is published by Scrivener Publishing. It encases the same contents as the previous edition. In the three years since the original launch of this book, it has received rave feedback from industry colleagues as “the book” for experienced professionals and amateurs alike. The book idea stemmed from my experience and the understanding of the great and unmet need expressed by the many professionals I was teaching over the years. This understanding led me to the journey of collecting and organizing this precious information in one consolidated place.

The creation of semi-solid formulations to be applied topically is an area that requires multiple disciplines. Sciences, such as chemistry, physics and biochemistry, must complement artistic and creative talents, and engage mathematical and engineering skills.

Professionals that work in this industry are typically armed with an education in at least one of the above areas and acquire additional proficiencies over time in their workplace. Therefore, many of those skills are obtained by trial and error and by learning from experienced mentors.

As noted, having taught skin product development for many years, I have been constantly approached, most often by students but occasionally by colleagues as well, as to why there is no adequate book to refer when either beginning to formulate topical products or when a need for problem-solving arises that requires a deeper understanding in a specific area. In times past, I have been sympathetic, but unable to offer a reasonable answer. Perhaps this lack of foundation, this muddy ability to give a straight answer is what, ultimately, compelled me to construct the book you now hold/or accessing online.

Compiling such a book is challenging. The main reason is that advice and guidance is typically communicated verbally from one professional to the other, in the same manner of loosely structured oral history—and it can be just as scattered. This book was created with the great collaboration of experienced and highly knowledgeable colleagues. It provides a comprehensive review of key elements in skin care product development and should serve as a basic guide for both beginners and advanced formulation chemists alike.

I sincerely thank my fellow contributors and hope that you, the reader, will find it valuable.

Nava Dayan PhD
Dr. Nava Dayan LLC
September 2016

Handbook of Formulating Dermal Applications

A Definitive Practical Guide

Preface

SECTION I:
Preliminary Considerations and Selection of Raw Materials

A Definitive Practical Guide

SECTION I:Preliminary Considerations and Selection of Raw Materials

SECTION I:
Preliminary Considerations and Selection of Raw Materials