Hydrophilic creams

Paspaleeva-Kuhn, V., and E. Nurnberg. 1992. Participation of Macrogolstearate 400 lamellar phases in hydrophilic creams and vesicles. Pharm Res 9 1336. 

Syed TA, Ahm AS, Holt AH et al. (1996) Management of psoriasis with Aloe vera extract in a hydrophilic cream a placebo-controlled, double-blind study. Tropical Medicine and International Health 1 505-509. 

Figure 18 Influence of different cream bases on the photostability of Retinoic Acid. A, Basis cream DAC B, hydrophilic ointment with water DAB C, nonionic hydrophilic cream DAB ...

Dermac SR-38 is one of a series of oxazolidinones, cyclic urethane compounds, evaluated as transdermal enhancers. The compound was designed to mimic natural skin lipids (such as ceramides), to be nonirritating, and to be rapidly cleared from the systemic circulation following absorption. In animal and human safety studies, Dermac SR-38 demonstrated a good skin tolerance (no observed irritancy or sensitization at levels of 1-10 wt% moderate to severe irritation in rabbit at 100%), and a low degree of acute toxicity (LD50(rat oral) > 5.0g/kg). The compound was evaluated for its ability to enhance the human skin permeation of diverse drugs from dermal and transdermal delivery systems. Data for minoxidil indicated an enhancer concentration-dependent effect for permeation enhancement. Dermac SR-38 was also found to enhance the skin retention of both retinoic acid when applied in Retin A cream, and dihydroxyacetone when applied in a hydrophilic cream. ... 

Regola, A. Canesi, M. Dolfini, A. Gazzaniga, A. Use of thermogravimetry in the physicochemical characterization of hydrophilic creams. Boll. Chim. Farm. 1996,135, 67-71. 

Tretinoin is usually applied as a 0.05% polyethylene glycol (PEG)-400/ethanol liquid or a 0.05% hydrophilic cream. Daily application results in inflammation, erythema, and peeling of the skin. After 3 to 4 weeks. pu.stular eruptions may be seen, causing the expulsion of microcomedones. Treatment may then be changed to applications every 2 or 3 day.s. Because the homy layer is thinned, the skin is mote susceptible to irritation by chemical or physical abuse. Thus, it is recommended that other kerolytic agents (.salicylic, sulfur, resorcinol, benxoyl peroxide) be discontinued before beginning treatment with tretinoin. 

Aloe vera extract 0.5% in a hydrophilic cream was shown to be more effective than placebo in treating psoriasis in a study involving 60 patients (Syed et al., 1996). Twenty-five of the thirty aloe patients compared with two of thirty placebo-treated patients were cured after 4 wk and a higher number of healed plaques were shown with aloe. No adverse effects or hypersensitivity reactions were noted. 

It should be mentioned that product formulation can also influence percutaneous absorption. An ointment vehicle with a high proportion of oils and fats is more likely to ensure skin penetration. A hydrophilic cream base is favorable to the absorption of more hydrophilic compounds. Skin hydration, which is achievable by the incorporation of humectants (e.g., glycerol) or by occluding dressings, can also be helpful. Particle size of substances that are not readily solubilized in the vehicle used must also be considered in developing the dermatological product. 

Tretonin cream, a topical retinoid, contains tretinoin 0.025% by weight in a hydrophilic cream vehicle of stearic acid, polyolprepolymer-2, isopropyl myristate, polyoxyl 40 stearate, propylene glycol, stearyl alcohol, xanthan gum, sorbic acid, butylated hydroxytoluene, and purified water. The tretinoin cream 0.02% contains the active ingredient tretinoin in a cream base. It is available at a concentration... 

Hydrophilic cream 0/w cream Nonionic hydrophilic cream SR DAC (Table 12.33), Lanette cream I and II (Table 12.34)... 

When the skin has become dryer and is changing to a subacute state it can further be treated with a hydrophilic cream. 

For patients with normal skin conditions and also for patients with a subacute dermatosis hydrophilic creams are frequently used. If a preparation with more fat is needed for a slightly drier skin, hydrophilic creams with a higher amount of lipophilic components are applied. For an example a cream with added soft paraffin (Table 12.4). 

Hydrophilic creams with a high amount of UpophiUc components are appropriate for the treatment of haemorrhoids. These creams cover the painful, damaged mucous membrane. Soft Paraffin Cetomacrogol cream FNA or Cream base DAC (Tables 12.4 and 12.6) are two examples for suitable bases. Thinner creams may flow off easily. A more HpophUic base is not desirable because of the chance on maceration the weakening of the skin by long time exposure to moisture. 

In general hydrophilic creams (o/w-creams) and emulsions are used without a bandage. Whether to cover the application site after application of lipophilic creams (w/o-creams) and ointments depends on the skin conditions. To soften a skin area with a strong keratinisation covering the lipophilic preparation with a bandage is effective. Fatty pastes and pastes with a cooling effect can be put on lint first. Thereafter the application site is dressed with a bandage. 

Another approach is that for hydrophilic creams the amount should be limited to as much as the skin can absorb. Lipophilic creams and hydrophobic ointments should be applied in a thin layer until the skin feels slightly fatty. 

Water easily evaporates from warm skin. Due to evaporation a cutaneous preparation looses its characteristics. To prevent water loss humectants are added. Humectants are non-volatile solvents that prevent water loss during storage as well as after application to the skin. Examples are propylene glycol, glycerol 85 % and sorbitol 70 %. Humectants are often used in cutaneous suspensions, hydrophilic creams and hydrogels. 

The activity of the preservative depends on the concentration in the aqueous phase and therefore on the partition coefficient (n-octanol/water). Because of its relatively favourable partition coefficient sorbic acid is a suitable preservative for o/w emulsions. Therefore it is often used in hydrophilic cream bases. Sorbic acid holds a carboxyl group that is deprotonated above pH 4—5. Sorbic acid only takes effect in the non-ionised form that means only in acidic solutions. However, at relatively low pH sorbic acid is degraded by oxidation. To prevent oxidation sorbic acid is often used in combination with potassium sorbate in order to obtain a pH value of 4-5. 

Dithranol is oxidised rapidly in aqueous bases. Usually, ascorbic acid is added to the aqueous phase of hydrophilic creams containing dithranol (Table 12.12). Salicylic acid is added to the lipophilic phase. In hydrophobic dermal bases the addition of just salicylic acid is sufficient. 

Cutaneous preparations can usually be stored at room temperature. In case of chemical instability or microbiological vulnerability storage in the fridge (2-8 °C) may be necessary. For example a hydrophilic cream with diltiazem hydrochloride for rectal application (Table 12.1) and preparations that contain tretinoin are kept at low temperature to reduce the degradation rate. A zinc oxide cutaneous suspension (Table 12.21) is microbiologically vulnerable and therefore has to be stored in the fridge. 

Control and recording of the total amount (important for hydrophilic creams, gels and alcohol containing formulations)... 

For the preparation method see Sect. 12.6.1.4. The preparation method resembles that of hydrophilic creams (see... 

A specific preparation method for cutaneous o/w emulsions is a dilution of hydrophilic creams. These are typically diluted in a ratio of 1 2 up to 1 6 with water (with added preservative), the ratio depending on the properties of the cream, the consistency that is desired and the location of application. Warming is not necessary for diluting the cream base with water. In some cases the use of arotor-stator-mixer is recommended to get finer emulsions and thereby a higher viscosity. 

Emulsions for cutaneous application are usually oil-in-water emulsions. The formulation resembles hydrophilic creams (see Sect. 12.7.10). The only difference is the higher content of water (Table 12.24). Water-in-oil emulsions are not common and therefore not described. 

By the addition of water the o/w emulsifying ointments are turned into hydrophilic creams with a relatively high content of lipophilic ingredients and good application properties (Table 12.4). Propylene glycol is added for preservation. 

Hydrophilic creams or o/w creams are emulsions whereby the outer phase is the aqueous phase. 

Hydrophilic creams are preferably formulated with combinations of emulsifying agents (mixed layer emulsifying agents or emulsifying agent complexes, see Sect. 18.4.3). For examples of o/w surfactants see Sect. 12.5.4. Generally hydrophilic creams may be anionic-active or non-ionic-active. Because of incompatibilities of active substances with anionic or non-ionic-active surfactants mixtures of these types of emulsiflers have to be avoided. The lipophilic excipients improve the consistency of the cream. These may be hydrocarbons such as white soft paraffin or waxes such as decyl oleate. 

The outer phase of hydrophilic creams consist of water, dissolved active substances, preservatives and humectants see Sect. 12.5.3. 

The formulation in Table 12.33 represents a non-ionic-active hydrophilic cream base. It contains a liquid wax (ethylhexyl laurate), which is well absorbed by the skin. The robust cream base tolerates processing of organic solvents and of phenols such as salicylic acid, in spite of its nonionic character. Lanette creams 12.34 are anionic-active bases. The two formulations differ in their consistency. The higher amount of emulsifying cetostearyl alcohol in Lanette cream II leads to a more stiff cream. It is especially suitable for preparations with a larger quantity of liquids. 

For the preparation of the hydrophilic cream base the excipients have to be divided into hydrophilic and lipophilic ones, forming the aqueous and lipophilic phase respectively. The aqueous phase consists of water, often sorbitol solution 70 %, glycerol 85 %, propylene glycol or sorbic acid and other dissolved substances as far as they are not volatile or degrade while being warmed. The lipophilic phase consists of fats, fatty oils, surfactant(s) and oil-soluble substances. The two phases are warmed separately to about 70-80 °C. The aqueous phase is added to the lipophilic phase, usually in one time or sometimes in portions. The mixture is stirred immediately after the addition and continued until the structure of the cream is built. Then stirring can be slowed down to prevent too much air being included in the cream. The evaporated water has to be compensated for. 

Aqueous pastes, also called hydrophilic pastes, consist of a hydrophilic base with 40-60 % solid substance. This type of paste may consist of water only, made viscous by a viscosity enhancer (see Table 12.41) or by the addition of a hydrophilic cream or emulsion. They are supposed to have a good absorptive capacity and are therefore used in the treatment of wetting skin disorders [59b]. 

With sterile lipophilic creams the cooled aqueous phase is added drop wise to the oil phase and mixed in aseptic circumstances. With sterile hydrophilic creams the preparation method should be planned as such that both phases are cooled to around 70 °C at the same time. The aqueous phase is aseptically processed with the oil phase to a hydrophilic... 

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