Revealing the Hidden Details of Nanostructure in a Pharmaceutical Cream

Abstract

Creams are multi-component semi-solid emulsions that find widespread utility across a wide range of pharmaceutical, cosmetic, and personal care products, and they also feature prominently in veterinary preparations and processed foodstuffs. The internal architectures of these systems, however, have to date been inferred largely through macroscopic and/or indirect experimental observations and so they are not well-characterized at the molecular level. Moreover, while their long-term stability and shelflife, and their aesthetics and functional utility are critically dependent upon their molecular structure, there is no real understanding yet of the structural mechanisms that underlie the potential destabilizing effects of additives like drugs, anti-oxidants or preservatives, and no structure-based rationale to guide product formulation. In the research reported here we sought to address these deficiencies, making particular use of small-angle neutron scattering and exploiting the device of H/D contrast variation, with complementary studies also performed using bright-field and polarised light microscopy, smallangle and wide-angle X-ray scattering, and steady-state shear rheology measurements. through the convolved findings from these studies we have secured a finely detailed picture of the molecular structure of creams based on Aqueous Cream BP, and our findings reveal that the structure is quite different from the generic picture of cream structure that is widely accepted and reproduced in textbooks. Oil-in-water creams are widely used in pharmaceutical products formulated to treat conditions like atopic dermatitis, rosacea and psoriasis 1. They also form the basis of veterinary medications used to assist wound-healing and treat skin infections 2 , and they are the basis too of a great many personal care products, spanning make-up foundations, anti-perspirants, sun lotions and deodorants 3. All such products are complex, multi-component colloids in which the constituent oil and water phases are stabilised through the addition of one or more ionic, non-ionic or zwitterionic surfactants, in combination with one or more co-surfactants (sometimes referred to as consistency enhancers) which might be long chain fatty acids, fatty alcohols or monoglycerides 4,5. Other components which might be added include humectants such as propylene glycol, anti-oxidants like α-tocopherol acetate, and preservatives like phenoxyethanol 6. The molecular architecture of any given cream formulation will clearly vary according to its chemical composition, and this in turn will determine its chemical and physical stability, and also impact the cream's sensory aesthetics and efficacy as a cosmetic, pharmaceutical, or veterinary product. Despite much research into the properties of creams and their many years of use, however, our understanding of their internal molecular structure is still far from complete, with the unavoidable consequence, therefore, that they are still formulated only in a semi-empirical manner. Junginger and co-workers 7 ...

The Influence of Co-Surfactants on Lamellar Liquid Crystal Structures Formed in Creams

“…In the studies reported here, we extend our investigations on model creams [ 3 , 12 ], investigating formulations based around the UK licensed, British Pharmacopoeial product, Aqueous Cream B.P. In keeping with Eccleston’s studies [ 11 , 16 ], we explore the consequences of changing the added co-surfactant on the molecular structure, rheology and stability of the creams and their corresponding ternary systems and elucidate the role of the co-surfactant alcohols in the gel network formation.…”

“…SANS measurements were made on one-day-old creams and their corresponding ternary systems as presented in Table 1 , with all samples prepared with all components protiated in D 2 O. Samples were loaded in purpose-built cells as reported previously [ 3 ] and measurements were made on the LoQ instrument at the ISIS pulsed neutron source (STFC Rutherford-Appleton Laboratory, Harwell Oxford, United Kingdom). For each sample, the SANS measurements were recorded at 298, 305, 310 and 318 K (± 0.1 K) with the sample environment temperature controlled using a Julabo water bath [ 21 ].…”

“…Although the SANS measurements on the formulations reported here were made on single preparations (as constrained by the neutron beam time awarded for the experiments), we have shown previously that the results obtained for replicate preparations of the creams are highly reproducible [ 3 ]. In the model-fitting of the SANS profiles, the quoted uncertainties on the fitted parameters represent the standard deviations on these estimates obtained from the variance-co-variance matrix in the least-squares optimisation, and where the model-fitting was performed with particular parameters fixed, these parameters are quoted without uncertainties.…”

“…The emulsions formed from immiscible oil and water phases are thermodynamically unstable and, as a means to improve their stability, so-called emulsifiers are added to reduce the interfacial tension. The emulsifiers added are generally mixtures of amphiphilic molecules, typically an ionic or non-ionic surfactant mixed with one or more co-surfactant(s) such as fatty alcohols, fatty acids or monoglycerides [ 3 , 4 , 5 ]. It is the combination of surfactant(s) with co-surfactant(s) in the emulsifiers that is essential for the formation of a cream; the use of surfactant(s) alone is insufficient.…”

“…In our previous studies on creams based around Aqueous Cream B.P. [ 3 , 12 ] we successfully revealed the microstructure of a system comprising water, liquid paraffin oil, sodium dodecyl sulfate (SDS) surfactant and an equimolar mixture of hexadecanol and octadecanol as co-surfactants. In both the aqueous creams and their corresponding oil-free ternary systems, we found that an excess of emulsifier (10% w/w) gave rise to a lamellar gel network phase.…”