Novel Delivery Systems to Solve Formulation Challenges

While There are many ways to deliver cosmetic actives to skincare , it is needless to say that Cosmetic chemists should do their research before selecting a particular cosmetic active delivery system. They should have in-depth knowledge about the physico-chemical considerations of the cosmetic active, its compatibility with raw materials selected to assemble the final formulation. In this article, Dr. Renuka Thergoankar provides a review of delivery system for cosmetic actives – some of them traditionally used , while some are new.

Cosmetics are defined as products meant to be poured, sprayed, sprinkled and rubbed on the skin for the purpose of cleanliness, changing appearance, protection and masking imperfection as per Drug and Cosmetic act. As per this definition the cosmetic products should ideally be topically applied and provide topical efficacy on the skin. But with increase consumer expectation and awareness the demands from the cosmetic products have increased. The modern consumer demands are:

Multifunctional properties,
Long lasting results
Convenient to use
Affordable price

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Starting from June 2020 Fragrance major Symrise is launching a joint research project with French research institute CRIEPPAM aimed at studying Lavender crop resilience, improved biodiversity and to generate valuable additional income for farmers. The CRIEPPAM research institute, local farmers and Symrise have been working towards increasingly cultivating lavender for several years. The project of CRIEPPAM and Symrise will identify the best inter-cropping options in lavender farming. This is expected to improve biodiversity, increase quality and quantity of lavender yield and lavandin essential oils. Symrise has also funded CRIEPPAM in developing the Espieur harvesting machine as part of its sustainability program. This machine is expected to pick only lavender blossoms — where the scent is concentrated — instead of stems, thereby saving 30 percent energy during steam distillation, while considerably increasing the quality of lavender essential oil.

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The availability of the actives to the skin can be enhanced by increasing the skin delivery. But the basic question still lies about Why to Enhance skin delivery? The skin delivery is generally enhanced to-

Achieve targeted & timed release of actives
Enhance efficacy
Provide effective concentration at the required site
To preserve the stability of actives
Minimize irritation potential

The enhanced skin delivery is generally achieved by delivery systems. A delivery system is the method of delivering active payloads on to the skin then having them pass through the lipid barrier and finally reaching the targeted lower layers beneath. An ideal delivery system generally is non toxic, carry the actives into substrate, provide controlled release of active, penetrate into the upper stratum corneum layer, improve formulations aesthetically, and allow easy handling of solid and liquid actives and it should be small enough to penetrate into the layers. There are several types of delivery systems which have gained popularity in cosmetic products in last few years. These are

Transdermal patches: Though these are present in the market for a long time but its use in the cosmetic market has not been completely explored. These help in providing targeted delivery of actives on the desired areas and help in giving the best effects. These are generally of two types:

Reservoir type and Matrix type

1. Thin Polymeric films

Vesicular Carriers: Liposomes, Niosomes, ethosomes, Nanoparticles, Nanoencapsulation, Nanoemulsions

Table 1: Commonly used delivery Systems

SNo	Delivery System	Description	Particle Diameter	Materials carried
1	Liposomes	Phospholipid based unilamellar or multilamellar bilayer vesicles	100-500nm	Hydrophillic & Hydrophobic actives
2	Nanodispersions	Phospholipid based cellular dispersion	100-500nm	Hydrophobic actives
3	Vesicles	Surfactant based Vesicles or micelles	100-500nm	Hydrophobic actives
4	Microencapsulates	Aldehyde crosslinked protein	100-5000 microns	Hydrophobic actives

But apart from these there are few systems which have suddenly started gaining popularity in recent times due to their efficacy, ease of penetration and cost.. These New delivery Systems are :

Chronospheres
Microsponges
Nanotopes
Penetration enhancers
Shear thinning lamellar gel network emulsions
Hydrophillic active filled Polyurethane Delivery system

Penetration Enhancers The ingredients which helps in increasing the penetration of actives in the skin without interacting with them or breaking the actives are called as penetration enhancers. These are generally of two types:
Chemical penetration enhancers: These are generally of chemical origin and are used to break the rigid structure of st. corneum. They alter the barrier properties of the skin by reversibly affecting the lipid bilayers or the protein

Generally the chemical enhancers are catagorised into two types depending on their interaction with lipids and proteins.

Compounds that interact with lipids eg Oleic acid, SLS
Substances that alter the protein structure in the corneocytes eg Urea, dimethyl sulfoxide, etc

A combination of hydrophilic and lypophilic penetration enhancers gives a synergistic enhancing effect.

Natural Penetration enhancers

In todays market with more emphasis on natural products these ingredients are more used. Natural topical permeation enhancers are developed to reach, stimulate, inhibit or compete with specific targets, covering a wide range of functionalities in skin care, hair care.

Example : Tetrahydropiperine

Mangiferine from Mango leaves

Nicotine from Tobacco leaves etc

Tetrahydropiperine

Derived from black pepper
Usage concentration- 0.01-0.1%
Non irritating and sensitizing
It’s a derivative structure of piperin
Enhances bioavailability and topical permeation of bioactive molecules

Mangiferrin from mango peel

Its a xanthonide, a chemical compound found in mangos.
This molecule is a natural phenol and shows antimicrobial and antioxidant activities
Used in age definening creams
Enhances bioavailability &topical
permeation of bioactive molecules

Thixogels

this superior cosmetic vehicle is a starch matrix encapsulation technology where in the O/W starch matrix is formed.In this Oil droplets coated with a polysaccharide shell are mixed with water, starch, oil and emulsifying agent. Corn starch slurry is prepared in cold water and Then heated up to starch dissolves. At 65 Degrees all oil phase ingredientents are added & the system is Homogenized to get a smooth thixogel. It is used for delivery of hydrophobic actives like AHA, retinoids and other fat soluble actives.

Chronospheres

Chronospheres are made by a blend of reactive prepolymers which are polymerized by ultravoilet light. These delivery systems can incorporate lipophilic and hydrophilic actives like hyluronic acid, PABA, salicylic acid etc in it. The delivery on skin happens in diffusion controlled manner. The INCI adopted name of these are acrylates/ carbamates copolymer. These are Biocompatible, temperature stable polymeric matrices in size range of 5 to 20 microns. These are generally used in deep moisturizing , skin lightening, sunscreening, anti ageing products

Image for illustration purpose only.

How is Skin allergy caused?

Microsponges

These are “Patented, highly cross-linked, porous, polymeric microspheres polymeric system consisting of porous microspheres that can entrap wide range of actives and then release them onto the skin over a time and in response to a trigger”. It consists of microporous beads, typically 10-25 microns in diameter, loaded with active agent which help in controlled release of these agents. The system is composed of methyl methacrylate/ ethylene glycol dimethacrylate is slower than styrene/ divinyl benzene system and the active is loaded in it by diffusion. The entrapped active is released when placed in contact with skin. These polymers are used in anti acne products ,Sun screens(Long lasting effect), anti dandruff eg selenium sulfide(Bad odour), colour cosmetics etc

Nanotopes

These are Generally used for delivery of vitamins E & A in anti ageing products

These ingredients are required in anti ageing products but its delivery to target area is a problem due to its stability, solubility and other issues.They are generally incorporated in the formulation by forming Nanotopes. Nanotopes are 20-40nm particles having lipid core covered by a membrane composed of phospholipids(Lecithin) and a cosurfactant (Polysorbate 80). The core Solution is usually CCTG or other fatty esters similar to it.

Vitamin E precursor-tocopheryl acetat is encapsulated in Nanotopes.The precursor is delivered into the skin where it is converted to Vitamin E, which acts as an antioxidant and free radical scavenger.

Vitamin A precursor retinyl palmitate which is encapsulated in Nanotopes,. The precursor is delivered into the skin and get converted to Vitamin A –which reduces the appearance of fine lines, age spots and wrinkles

Shear thinning lamellar gel network

It is an emulsion system consisting of non conventional emulsion stabilizers

Here sodium stearyl phthalamate (1% to 1.5%) used with low HLB emulsifiers and an anionic polymeric emulsifier(acrylate C10-30 ALKYL ARYL CROSSPOLYMER)IN 5: 1ratio. This forms a lamellar gel network which provides enhanced stability & superior asthetics. It Provides better hydration on skin by forming a protective barrier. It also Enhances SPF in sunscreen formulation specially for high SPF products with higher percentage of TiO2 and ZnO. This system can also be used in formulating sprayable products

Hydrophillic active filled Polyurethane delivery system

Used for pre moistened towlettes, dry cleansing wipes etc
The hydrophilic polyurethane resins prepared by reacting a diol component, an organic chain extender and an organic diisocyanate
The diol component is at least one of (1) a long chain poly(oxyethylene) glycol of molecular weight above 2500 and (2) a medium chain poly(oxyethylene) glycol or polyester glycol of 250-2500 molecular weight.
These hydrophilic polyurethane resins work as carrier vehicles for various active agents including a medicament, fragrance, flavor, sun-screen, depilatory, cosmetic.
Generally the wipes used in the industry have to be wetted separately whereas with this system we can mix the actives directly with the fibers as they can absorb any amount of vehicle due to its fibrous structure

Apart from these there are several delivery systems which can be used in the development of cost effective efficacious products. Hence the industry should look at delivery agents as quality enhancing cost reducing agent rather then cost enhancing agent.