Handbook of Formulating Dermal Applications E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
The conceptualization and formulation of skin care products intended for topical use is a multifaceted and evolving area of science. Formulators must account for myriad skin types, emerging opportunities for product development as well as a very temperamental retail market. Originally published as "Apply Topically" in 2013 (now out of print), this reissued detailed and comprehensive handbook offers a practical approach to the formulation chemist's day-to-day endeavors by: * Addressing the innumerable challenges facing the chemist both in design and at the bench, such as formulating with/for specific properties; formulation, processing and production techniques; sensory and elegancy; stability and preservation; color cosmetics; sunscreens; * Offering valuable guidance to troubleshooting issues regarding ingredient selection and interaction, regulatory concerns that must be addressed early in development, and the extrapolation of preservative systems, fragrances, stability and texture aids; * Exploring the advantages and limitations of raw materials; * Addressing scale-up and pilot production process and concerns; * Testing and Measurements Methods. The 22 chapters written by industry experts such as Roger L. McMullen, Paul Thau, Hemi Nae, Ada Polla, Howard Epstein, Joseph Albanese, Mark Chandler, Steve Herman, Gary Kelm, Patricia Aikens, and Sam Shefer, along with many others, give the reader and user the ultimate handbook on topical product development.
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Contents
Cover
Title page
Copyright page
Preface
Section I: Preliminary Considerations and Selection of Raw Materials
Chapter 1: Pre-formulation Design and Considerations
Introduction
Project Goals and Formulation Design
Selecting The Right Ingredients for Your Design
Pre-formulation Considerations—Vehicle Examples
Choosing a Surfactant
Selecting a Suitable Emulsifier
Other Pre-formulation Considerations
Botanicals
Choice of Preservation Systems
Manufacturing Considerations
Reading a Technical Product Sheet
Regulatory Considerations
Safety of the Formulation
Summary
Chapter 2: The Use of Thickeners in Topically Applied Formulations
Introduction
Rheology
Classifying Thickeners
Advantages and Disadvantages of Natural Thickeners
Inorganic Thickeners
Formulating With Thickeners
Further Example Formulations
Summary
Chapter 3: The Incorporation of Delivery Systems into Topical Formulations: A Case Study on the Use of Salicylic Acid for Acne Treatment
Abstract
Background
Motivation For Encapsulaton Of Salicylic Acid
Formulations With Sa And Encapsulation Technologies
Summary/Conclusion And Future Perspectives
Chapter 4: Formulating Skin Care Products with Silicones: Approaches and Strategies
Introduction to Silicones
Major Categories of Silicones and Their Properties
Silicone Applications and Benefits in Personal Care Formulations
Moisturizers (Hand and Body Lotions)
Facial Care (Anti-aging Products)
Color Cosmetics
Sun Protection
Shampoos
Hair Conditioners
Skin Cleansers and Body Washes
Antiperspirants and Deodorants
Formulation Considerations
Formulary
CATEGORY: Moisturizers
CATEGORY: Face Care Formulations
CATEGORY: Color Cosmetics
CATEGORY: Sunscreens
CATEGORY: Antiperspirants
CATEGORY: Cleansers and Shampoos
CATEGORY: Hair Conditioners
Summary
Chapter 5: The Use of Corn-derived Ingredients in Personal Care Applications
Introduction
Zea Mays (Corn) Starch
Modified Starches
Hydrolyzed Corn Starches
Additional Applications for Corn-derived Ingredients in Topical Formulations
Summary
Section II: Formulation, Processing and Production Techniques
Chapter 6: Emulsions and their Characterization by Texture Profile Analysis
Introduction
Basic Principles of Emulsion Technology
Phenomena Involved in Emulsion Instability
Mechanisms of Emulsion Stabilization by Emulsifiers
Measurement of Emulsion Stability
Definitions of Key Phenomena in Emulsion Technology
Sensorial and Textural Properties of Emulsions
Texture Profile Analysis (TPA)
Determination of Textural Attributes from Texture Profile Analysis
Analysis of Commercial Lotions and Creams by Texture Profile Analysis
Analysis of O/W Emulsions by Texture Profile Analysis
Concluding Remarks
Acknowledgements
Chapter 7: High Internal Phase Water-in-oil Emulsions
Introduction
High Internal Phase Water-in-oil Emulsions (HIPEs)
Stabilization in HIPEs
Topical Delivery Systems Based Upon HIPEs
Future Prospects for HIPEs
Summary
Chapter 8: Manufacturing Topical Formulations: Scale-up from Lab to Pilot Production
Introduction
Overview of Key Scale-up Considerations
Process Design
Scale-up Principles
Quality by Design Principles
Anchor Speed
Disperser Speed
Mixing Time
Mix Temperature
Vacuum Pressure
Transfer Pressure
Experimental Design
Process Equipment: Pilot Scale
Formulation Specific Requirements
Filling & In-process Analytical Equipment
Facilities and Engineering Issues
Raw Material Considerations
Summary
Chapter 9: Foam: A Unique Delivery Vehicle for Topically Applied Formulations
Introduction
Overview of the Market: Current Foam Technologies
The Rosetta Stone Of Foam
Water-containing Foams
Nanoemulsion Foam
Hydroethanolic Foam
Potent Solvent Foam
Water-free Foams
How to Formulate Foam Products
Methods of Evaluation of Foam Products
Summary
Section III: Testing and Measurements Methods
Chapter 10: Using Experimental Design to Optimize Formulations
Introduction
What is Experimental Design?
Factorial Designs
Mixture Designs
Mixture/Amount Design
Exactly What Is Synergy?
The Cornell Approach
How To Get Started
Example
JMP Leverage Plots
Additional Thoughts
Conclusions
Chapter 11: Rheological Properties of Topical Formulations
Introduction
Rheological Measurements
Instrumentation
Rheological Additives
Formulation of Topical Products
Summary
Chapter 12: Viscosity Measurement for Topically Applied Formulations
Introduction
Definitions and Units of Viscosity
Importance of Shear Rate
The Stages in Product Development for the Consideration of Viscosity Evaluation
Instrumentation for Measurement
Reading and Understanding Viscosity Specifications
Measurement Key Considerations
Summary
Chapter 13: Fourier Transform Infrared (FTIR) Spectroscopic Imaging Analysis of Topical Formulations
Introduction
Experimental Methods
Imaging Formulations: Examples
Summary
Section IV: Sensory and Elegancy
Chapter 14: Creating Appealing Topically Applied Formulations: Linking Physical Aspects to Marketing Psychology
Introduction
Luxury Goods Business
Consumer Perception—Multiple Factors At Play
Matching the Product to the Consumer
Sustained Success
Research That Changed Everything
The Challenge of Matching Sensorial Attributes
Selecting Ingredients for a Novel Approach
Real Security
Combining Elements of Development
Involving Scale-up and Manufacturing
Time Scale
Summary
Chapter 15: The Use of Fragrance in Topically Applied Formulations
Introduction
Aroma Chemicals
Natural Products
Terpenes: Where Nature and Chemistry Collide
Natural and Organic Fragrances
Hydroalcoholics
The Importance of Weak Forces
Emulsion Systems
Surfactant Systems
Controlled Release
Malodor
Regulatory Essentials
Aromascience
Summary
Section V: Stability and Preservation
Chapter 16: Stability Testing for Topical Formulation Development
Introduction
Types of Topically Applied Products
Product Instability
Considerations
Chemical Stability Measurements
Physical Stability Measurements
Summary
Chapter 17: Preservation of Topical Formulations: An Historical and Practical Overview
Historical Perspective on Microbiology and Preservation in Personal Products
Preservative Types and Their Usage in Personal Care Products
Isothiazolinones
Halogenated Preservatives
Other Preservatives
Non-classified Preservatives (non-regulated)
Final Words
Chapter 18: Microbiological Stability for Skin Care Formulations
Introduction
Preservation Of Topical Formulations – Defining The Purpose
Types And Classes Of Preservatives
Formulation Design And Preservation
Preservative Blends
Natural Preservatives
Preservative Efficacy Testing
Ensuring Preservative Stability
Regulatory And Safety Aspects Of Preservative Use In Cosmetics
Summary
Section VI: Color Cosmetics
Chapter 19: Lip Care Product Formulation Strategies
Types of Lip Products
Setting Specifications and Path of Development
Ingredients
Pigment Dispersants/Emulsifiers
Common Formulation Challenges
Physical Stability Requirements
Processing
Packaging
Summary and the Future Perspective of Lip Care Formulations
Chapter 20: Formulation of Nail Care Products
Introduction
Nail Lacquer Chemistry and Formulation
Nail Lacquer Testing
Nail Lacquer Manufacture and Quality Control
Nail Lacquer Packages
Non-lacquer Nail Products
Summary
Section VII: Sunscreens
Chapter 21: Formulation of Sunscreens in the United States
Introduction
SPF and UVA Protection in Sunscreen
Determination of SPF
High SPF
UVA Protection
Broad Spectrum Protection and Prevention of Skin Damage
Ingredients and Formulation Strategies
Product Forms
Key Formulation Considerations
New Active Ingredients on the Horizon
Summary
Chapter 22: Formulating a Day Cream with SPF: A Case Study
Introduction
Background
UV Damage
Sunscreens: An Overview
Formulation Considerations
Summary: Our Final Formulation
Glossary of Terms, by Chapter
Author Biographies
Index
End User License Agreement
Guide
Cover
Copyright
Contents
Section I: Preliminary Considerations and Selection of Raw Materials
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.
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener([email protected])Phillip Carmical ([email protected])
Handbook of Formulating Dermal Applications
A Definitive Practical Guide
Edited by
Nava Dayan
Copyright © 2017 by Scrivener Publishing LLC. All rights reserved.
Co-published by John Wiley & Sons, Inc. Hoboken, New Jersey, and Scrivener Publishing LLC, Beverly, Massachusetts. Published simultaneously in Canada.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002.
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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
SECTION I:Preliminary Considerations and Selection of Raw Materials
CHAPTER 1Pre-formulation Design and Considerations
Howard Epstein, PhD
EMD Chemicals
Key Words
Oil-in-Water Emulsification, Water-in-Oil Emulsification, Emulsifier Quaternary, Formulation Design, Global Intellectual Property, Marker Compounds, Oil/Water (octanol) Partition Coefficient, Anionic / Cationic / Amphoteric / Nonionic Sufactants, Tyrosinase
Introduction
The novice formulation chemist may be overwhelmed when challenged with developing a topical product suitable for a local or global market. The basic questions that come to mind are: Where does one start? What criteria should a formulation chemist consider when selecting the ingredients to incorporate into a new product? How are safety and product performance claims established in different countries? What are the criteria for a patent? How does one ensure a patented formulation is not inadvertently being violated? Are any ingredients in the new formulation incorporated at levels restricted in a respective country where the formulation will be sold? The ability to freely exchange information globally via the internet is a blessing and a curse. It is a blessing to have the ability to communicate and research information instantaneously and to conduct preliminary research conveniently from the desk prior to starting formulation activities. The curse is that the seeker of reliable information must have the ability to discriminate between opinion, facts and misinformation when accessing information from this resource.
This chapter is aimed at providing guidance to formulation chemists and other professionals involved in skin care product development, assisting them to produce innovative products. The goal is to provide insight with respect to planning and executing formulation development in an efficient and cost-effective process that is well-planned and intelligently executed.
Project Goals and Formulation Design
Prior to initiating project activity at the bench, a detailed description of the product design plan should be written. The project design sheet should provide a brief description of the project, including relevant background information of the rationale for the product. Product concept, goals, and objectives should be stated. The project description should contain the value proposition to the consumer, i.e., a statement of benefits that will be delivered by the product. It should include answers to the following questions: what unmet consumer need or needs will the new formulation provide and what is the formulation’s cost constraints? Regulatory and other constraints should also be considered during the early phase in the design sheet. A thorough product description will assist the formulation chemist in the determination of appropriate technologies for consideration. The following product design checklist describes the types of questions a formulation chemist must satisfy before pressing forward on a potentially viable project:
Project objective is clear and the concept and goals are stated.
Value proposition is clear; benefit provided to the consumer is stated, budget for project is specified.
Distribution (limited vs. global) is determined.
Budget limitations are identified and isolated.
Desired technologies are described in general terms.
Desired claims for the product are defined; what is this product’s end game?
Target site of application is determined (i.e. the hair, face, body, or a combination of sites).
An intellectual property search is conducted, where in known regulatory and patent restrictions are identified.
Potential market analysis observations are conducted.
Once these questions have been considered and given a preliminary response, a product design flow will begin to form, following the logical tenets of initial formulative product scale-up. Such a workflow is shown in the following diagram:
Fleshing out a product design plan requires both satisfactory detail and the formulation chemist’s willingness to address tough and complex questions. Table 1 offers an example planning sheet for an SPF product, along with further questions the chemist must consider in pursuing the process.
Table 1.Cosmetic Ingredient Reference Sources
Reference Source
Publisher
I
nternational
C
osmetic
I
ngredient
D
ictionary and
H
andbook
Personal Care Products Council, Washington, DC
B
ritish
P
harmacopoeia
The British Pharmacopoeia London
Title 21 of the U.S. C
ode of
F
ederal
R
egulations
, concerning food and drugs
United States Government
United States Patent and Trademark Office
United States Government
California Proposition 65
State of California
European Parliament Regulation EC No. 1223/2009
In effect as of July 2013. Addresses protection of human health by regulating cosmetic products. This legislation impacts products imported into the EU.
C
osmetic
I
ngredient
R
eview
Personal Care Products Council, Washington, DC
H
andbook of
C
osmetic
S
cience and
T
echnology
Informa Healthcare, New York. Provides general information on all aspects of cosmetic science and technology.
C
osmetic
S
cience and
T
echnology
Marcel Dekker, Inc., New York. A series of textbooks, each reviewing different topics in the field of cosmetic technology.
R
emington:
T
he
S
cience and
P
ractice of
P
harmacy
Lippincott Williams & Wilkins, MD, USA. An excellent resource for information for formulation bases for cosmetic and pharmaceutical products.
H
arry’s
C
osmeticology
Chemical Publishing Company, MA, USA. Several chapters of information covering all aspects of cosmetic science and technology.
Referencing the project design sheet, an intellectual property (IP) search should be conducted early on in the development stage. If the product is intended to be globally distributed, the formulation chemist should be familiar with the IP requirements of each region of the globe in which the product is intended for sale. For communication and assistance in the United States, the US Patent and Trademark Office (USPTO) can provide information regarding establishing and protecting IP.1 An Intellectual Property Rights (IPR) Toolkit for protecting intellectual property rights overseas is likewise available from the USPTO.2 The World Intellectual Property Organization (WIPO) is another valuable resource to obtain IP global information.3 Varying regulatory requirements can impact selection of ingredients, product claims and safety assessment. For example, China has a “positive list” of ingredients that may be used. Ingredients not listed will require a petition for approval, a process that is highly complicated and costly.4 A complete battery of safety testing may be required by China utilizing animal testing. In contrast, the European Economic Union countries issued the 7th amendment to the EU Directive that bans animal testing of cosmetic ingredients and/or finished formulations.5
Product Design Workflow Diagram
Selecting The Right Ingredients for Your Design
Prototype starting formulations may be easily found in a variety of sources, such as the websites for ingredient suppliers’ databases, trade magazines, and numerous textbooks, both online and in print. These formulations are frequently untested for their physical chemical properties, stability or interaction with the skin, and are intended to be used mainly for reference purposes. They may not be stable, adequately preserved, or optimized with respect to elegancy and performance. Their development is often limited and does not consider the optimal delivery of an “active” compound to desired skin or hair targets. Critical factors for formulation development should be considered when selecting the vehicle for the product that is the most appropriate when determining the project goal.
An active ingredient is incorporated into a carrier which is typically a mixture of ingredients that provide the product with its consistency. The carrier is referred to as a vehicle responsible for delivering the active ingredient into the skin. Topical product vehicles may be categorized by their intended us as follows: cleansing, decoration, care of skin, nails, and hair, hydration, and protection.6 Classification of vehicles may be designed by function; shampoo or hair colorants for hair, polish or lacquer for nails, toothpaste, lipstick or lip-protection for the mouth, moisturizers, body lotion, aftershave, antiperspirant/deodorant (AP/DEO), and sunscreen. Sensory feel and the chemical nature of the ingredients to be used will impact the decision to formulate in either o/w or w/o emulsion systems. The polarity of lipid components will also influence the selection of the emulsifier. To illustrate, microemulsions are small droplet size (5-50 nm) stable emulsions and may be considered when one desires to dissolve active substances with enhanced skin penetration and permeation or when certain components in the formulation should be protected for stability.6 More recently the use of nano-emulsions, defined as emulsions with a particle size between 20–200 nm with a narrow distribution droplet size range, have become a popular approach for formulating more effective and elegant cosmetic products. In the European Union, products containing nanomaterials are required to be noted on the product label with the statement “contains noanomaterials.”5 At of this publication, no such requirement exists in the United States.
Pre-formulation Considerations—Vehicle Examples
Emulsions are the most common forms of vehicles for skin care products. Various emulsion types are available. Aqueous gels, w/o, o/w, and silicone-in-water (s/w), multiple emulsions, microemulsions, and nanoemulsions are a few examples. Selection of the emulsification system will determine the nature of the system. It is possible that certain emulsifiers having an identical designated chemical name in the International Nomenclature of Cosmetic Ingredient (INCI) Dictionary sourced from different suppliers will have a slightly different chemical composition.7 For this reason, formulation chemists should keep records of the source of ingredients and maintain a current specification sheet for each ingredient in the formulation as the project is initiated at the bench. If, for example, the product is targeted for children or for people with sensitive skin the selection of ingredients, particularly emulsifying agents, becomes increasingly important. Further considerations include application to the body site of intended use; what “time” the product is designed to be used (i.e., day vs. night cream); will clothing or bedroom pillowcases and sheets come into contact with the product; will other products be applied over or under the product? Table 1 contains a list of resources available to identify common ingredients in topical formulations, their function, source of supply and other useful information for formulation chemists.
Choosing a Surfactant
Surfactants can be classified according to their charge being: anionic, cationic, amphoteric, or nonionic. Selection of the most appropriate surfactant will depend on a variety of considerations, including the purpose of the formulation, aesthetic considerations, the other ingredients to be formulated in the product, and the product form. Once the chemical class is selected the formulation chemist can select a surfactant or a combination of surfactants. Typically high surfactant solubility is desired for cleansing products, whereas medium solubility is required for emulsion spreading. Surfactants with low solubility in water can be formulated in w/o emulsions. A blend of surfactants is usually utilized for o/w emulsions. A surfactant molecule has a water-soluble component and an oil-soluble component. In an emulsion, these molecules reduce the interfacial thermodynamic tension at the water and oil phase, a process that lowers the energy needed to mix the oil into the water. Adding a surfactant therefore makes the emulsification possible, i.e., for the oil to disperse into the water phase as a discrete droplet. Each droplet is surrounded by a molecular layer of surfactant molecules around it which helps prevent the droplets around it from fusion and keeps them dispersed as distinct entities in the water.8 Many resources are available to assist with the determination of the optimal selection of surfactants.8-12 The Hydrophilic-Lipophilic Balance (HLB) system is a popular method used in the selection of the optimal emulsifier.10 Formulation chemists should note that while the HLB system was designed for the evaluation of ethoxylated, nonionic emulsifiers, it may be applicable for the use of nonionic surfactants and should be used with caution in these cases. The HLB evaluation may not be as accurate for formulations containing ionic emulsifiers. Further, the required HLB is likely to change when the level of neutralizing agents, including triethanolamine, sodium oleate or potassium oleate are incorporated into the formulation. In these situations, it is advisable to monitor stability closely for signs of stability failure. These signs may be phase separation, color changes, pH changes, and viscosity changes.
Selecting a Suitable Emulsifier
Emulsifiers can act as solubilizers, and as spreading or dispersing agents. Selection of the appropriate emulsifier enables one to formulate homogeneous mixtures, allowing the dispersion of agents ordinarily difficult to disperse, and for oil phases to be mixed with water. Not all emulsifiers behave in the same way. The properties of a given emulsifier may dictate the emulsion type. Moreover, the emulsifying agent will impact the desired sensory properties of the product including color, odor, and consistency.
Nonionic emulsifiers are frequently selected to emulsify fats, oils, waxes, and powder suspensions. They may be suitable when the formulation requires high levels of electrolytes, acidic or basic formulations with a pH ranging roughly between 4 and 8 and good stability in hot environments and hydroalcoholic systems. Mild quaternary emulsifiers may be selected for formulations having an extreme pH, hair conditioning products, emulsification of silicones, and structural agents for anhydrous sticks. Ethnic hair care products, for example, frequently require formulation at a pH range of 12-14. Therefore, a well-designed plan should include the following parameters: surfactants that can be considered, and emollients that can be used at that high level of pH, ensuring long-term stability. For formulations with a pH ranging between 4.0 and 7.0, but not above 8.0, stearyl alcohols and synthetic waxes will provide good compatibility with oils and should exhibit good batch-to-batch consistency. Polysorbates are the optimal surfactants for emulsification systems that contain waxes, silicones and solubilizing agents in o/w emulsions for hair, skin moisturizers, and skin cleansing formulations, while sun care formulations and long-wear lipsticks benefit from the use of rinse-off resistant ingredients, such as silicone, silicone derivatives, and ethylcellulose polymers. A variety of formulation approaches are possible to achieve water- or wash-off resistance. For sunscreen formulations, choosing a w/o system will assist in reducing the occurrence of re-emulsification of the product when applied to skin, along with subsequent exposure to water. Emulsions using hydrophilic emulsifiers are useful for this purpose.13-15 Polyoxyethylene sorbitan monooleates and monostearates are common examples of hydrophilic emulsifiers. Long-wear and water-resistant properties for lipsticks and sunscreen formulations can be achieved by using silicone oils and film forming polymers. For these requirements, sucrose distearates are another optional class of ingredients. Phosphate esters can be used to assist in keeping a shampoo clear and stable, reducing the probability for precipitation developing, as may occur over time. For boosting foam in shampoos, enhancing skin feel, or modifying the viscosity of frequent-use products, amphoteric surfactants may be an option. Amphoterics are frequently used in baby formulations, because they are associated with low potential for irritation to skin, as exemplified by Johnson & Johnson’s “No More Tears” Baby Shampoo.
Other Pre-formulation Considerations
A formulation intended to enhance percutaneous absorption requires that the formulation chemist consider the physical chemical properties of the active compound to be used so that an initial prediction can be assessed. Molecular weight in the range of 500 daltons, and thus appropriate for skin penetration and lipophilicity, may be expressed by calculating the octanol/water partition coefficient. Properties of the vehicle are another key factor, as these properties may either enhance or retard penetration. Particle size, pH in water, stability, and potential incompatibility of the actives and other ingredients should be considered at the pre-formulation stage as well. The chemical nature of the ingredients in the formulation may be impacted by the type of claims sought and the consequent testing required in order to validate the claim. (The reader is here referred back to the project evaluation process example as shown in Table 1.) Again, the formulation chemist should consider this possibility during the pre-formulation stage. In the design of sunscreen
