www.chemicalsknowledgehub.com
Topical drug formulation: the challenges and new solutions
By Ralph Landau, Head of Development, Cambrex Whippany, Cambrex Corporation
Drug product formulation is a complex endeavour and every formulation presents unique development and manufacturing challenges that will vary based on the type of drug and the method of administration. Here, the particular challenges facing formulators of topical drugs are discussed and ways of addressing these are presented.
T
opical drugs are prescription or over-the-counter (OTC) dermatological drugs or pain medicines that are
manufactured as lotions, creams, foams, solutions, suspensions or gels. They are classed as a semi- solid drug product based on their composition of water, oil, the active pharmaceutical ingredient (API) and other ingredients such as thickening or gelling agents, emulsifiers, preservatives, antioxidants and solvents. This type of formulation is particularly challenging because it requires specific consistency and stability, and aligning the mechanism of action and sensory characteristics can be challenging. In addition, like liquid formulations, topical drugs are typically less stable and have a shorter shelf life than solid dosage forms. The mechanism of action pertains to the intended use of the topical, and whether it is meant to treat the surface of the skin by penetrating to a certain layer of the dermis, or into muscle tissues, as with pain-relieving drugs. A topical should be easy to apply and have a composition appropriate to the needs of the product. From a sensory perspective, a topical should have a good texture (also known as skin feel), appearance and smell that should not change during the documented shelf life of the product.
Getting into the skin
Topical formulations can be applied to treat a range of dermatological indications including dermatitis, eczema, pain, psoriasis, antimicrobial treatment/infection,
Summer 2020 Ralph Landau
diabetic ulcers and acne. In addition to an appropriate composition and texture, a topical should be easy to apply and not cause irritation. While this may sound simple, it requires a concentrated development work focused on five key physical characteristics:
1. Homogeneity 2. Particle distribution 3. Grittiness 4. Spreadability (ease of application vs tendency to drip) 5. Need for surfactants
The viscosity of a topical has a strong impact on skin feel and will help to determine how a topical is classified, in addition to all five of the key physical characteristics listed. Ointments are made without an aqueous phase and have the thickest feel of all the topical drug types. Gels are made without an organic phase and tend to have the lightest feel. Creams and lotions are emulsions, the only real difference between them being their viscosity, creams being thicker than lotions.
The choice between formulating a product as an ointment, lotion, cream or gel is driven by the indication, including what area of the body is being treated and the frequency of application. It can also be driven by market forces. For example, just as a tablet is not considered equivalent to a capsule, the various types of topical dosages are also considered to be different from each other, which means a generic of ‘Brand A’s’ lotion could not fill a prescription for ‘Brand A’s’ cream. Therefore many companies will introduce topical line extensions in a new topical dosage form in order to remain exclusive. Determining whether the API needs to act on the skin surface or whether it should be absorbed into the skin is critical in the choice of formulation as there are ingredients that encourage or discourage penetration.
Quality process for quality products Drug product formulation success relies on batch-to-batch consistency and the reliability of the process and of the product. Somewhat unique to topical drugs is the property of viscosity. Many processing factors can affect the final viscosity, including mixing speed and duration as well as small changes in composition, particularly of thickening agents. Viscosity is a critical variable to control in topicals because it is related to drug delivery rate.
When manufacturing bulk powder for tablets or capsules, the time of mixing (for example in a V-blender) has very little
A topical should be easy to apply and have a composition appropriate to the needs of the product. From a sensory perspective, a topical should have a good texture (also known as skin feel), appearance and smell that should not change during the documented shelf life of the product
impact if the mixing is continued an extra hour after homogeneity is achieved. However, semi-solids can experience significant viscosity changes (shear-thinning or shear thickening phenomena) if process variables are not tightly controlled. Whether working with prescription topical drugs or OTC products, there is a need to achieve the exact same texture, viscosity and homogeneity across batches. This not only affects the clinical performance of products, but also affects the patient experience when the patient applies the topical. Products with variable viscosity tend to receive more customer complaints.
Even the smallest of details can impact the critical quality attributes
33
Topical Products
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60
