Semisolid creams

Is a local or systemic effect required This will influence, for example, the choice between a traditional dosage form, such as a semisolid cream or gel, and a system that promotes increased intravaginal residence, with a concomitant increased possibility of absorption across vaginal epithelium, for example, from intravaginal ring (IVR) systems or systems utilizing a bioadhesive polymer component. 

Figure 7.20 Schematic diagram of a typical semisolid cream prepared with cetostearyl alcohol and ionic surfactant. Note the four phases (1) the dispersed oil phase (2) the crystalline gel phase containing interlamellar-fixed water (3) phase composed of crystalline hydrates of cetostearyl alcohol (4) bulk water phase.

Topicals— These are semisolid preparations such as creams, ointments, or gels intended to be applied to the skin or certain mucous membranes... 

To be semisolid, a system must have a three-dimensional structure that is sufficient to impart solidlike character to the undistributed system that is easily broken down and realigned under an applied force. The semisolid systems used pharmaceutically include ointments and solidified w/o emulsion variants thereof, pastes, o/w creams with solidified internal phases, o/w creams with fluid internal phases, gels, and rigid foams. The natures of the underlying structures differ remarkably across all these systems, but all share the property that their structures are easily broken down, rearranged, and reformed. Only to the extent that one understands the structural sources of these systems does one understand them at all. 

Creams are semisolid emulsion systems having a creamy appearance as the result of reflection of light from their emulsified phases. This contrasts them with simple ointments, which are translucent. Little agreement exists among professionals as to what constitutes a cream, and thus the term has been applied both to absorption bases containing emulsified water (w/o emulsions) and to semisolid o/w systems, which are physicochemically totally different, strictly because of their similar creamy appearances. Logically, classification of these systems should be based on their physical natures, in which case absorption bases would be ointments and the term cream could be reserved exclusively for semisolid o/w systems, which in all instances derive their structures from their emulsifiers and internal phases. 

The amounts of ointments and creams people apply are highly individualized. So are the techniques of application. Some patients vigorously rub semisolid formulations into the skin, while others just spread films until they are more or less uniform over the desired area. While pharmacokinetic assessments of a system s delivery attributes is ordinarily done using normal skin (in vitro) or on healthy volunteers (in vivo), the site of its clinical deployment is usually anything but normal. Rather, it is determined by the skin condition to be treated. Clearly, the manufacturer is without control over how a disease is expressed in a particular patient. For many diseases, disease manifestation can be anywhere on the body. Moreover, from individual to individual it varies in intensity and vastness. Thus, more area may be involved in one case than in another, and the barrier function of the skin may be more or less intact in any instance. This creates a set of imponderables with respect to delivery, efficacy, and safety. 

Calculations Involving Ointments, Creams, and Other Semisolids... 

The present chapter deals with calculations involving topical semisolid dosage forms, which include ointments, creams, and pastes. 

Creams are semisolid preparations meant for external application as emollients or as topical medications. They are semisolid emulsions of either the oil-in-water or the water-in-oil type. 

Pastes are also semisolid preparations intended for external application to the skin, and differ from ointments and creams in that they contain a high solid content. Pastes are made stiff by the addition of powders such as starch, zinc oxide, calcium carbonate or their mixtures. 

CHAPTER 7 CALCULATIONS INVOLVING OINTMENTS, CREAMS, AND OTHER SEMISOLIDS... 

SLN for the topical application to the skin are made np from lipids such as glyceryl behenate (Compritol 888 ATO), glyceryl monostearate (Imwitor 900), glyceryl pahnitostearate (Precirol ATO 5), triglycerides (trimyristin, tripalmitin, tristearin), or the wax cetyl pahnitate. Nanodispersions contain 5 to 40% lipid the higher-concentrated preparations have a semisolid appearance. These nanodispersions are cosmetically acceptable as they are, whereas the fluid nanodispersions with lower lipid content shonld be incorporated into, for example, a cream that facilitates the application. 

The generally low lipid content and the poor viscosity of lipid nanodispersions make these preparations, as they are, less suitable for dermal drug application. The handling of the preparation by the patient is improved by SLN incorporation into ointments, creams, and gels. Alternatively, ready-to-use preparations may be obtained by one-step production, increasing the lipid phase to at least 30%. However, increasing the lipid frequently results in an unwanted increase in particle size. Surprisingly, it has been found that very concentrated (30 to 40%) semisolid cetyl palmitate formulations preserve the colloidal particle size [10]. 

The presence and state of solid lipid nanoparticles incorporated into semisolid formulations have also been investigated by DSC [77,83,84]. Using this method, de Vringer and de Ronde were able to draw conclusions on the preparation-dependent distribution of the matrix lipid of their particles in the different phases of a cream formulation [77]. 

Creams are semisolid preparation (usually emulsion) for external use. They are oily and non-greasy in nature. 

Oral liquid and semisolid formulations containing water as part of the vehicle may be prone to microbial spoilage in the absence of a preservative. In the case of pharmaceutical creams, these are usually oil-in-water emulsions stabilized using a surfactant. Phenolic preservatives, e.g., parabens esters, are inactivated in the presence of nonionic surfactants, and this detrimental interaction can have serious consequences for preservation of the product (20). 

Creams/Lotions Semisolid emulsions that contain fully dissolved or suspended drug substances for external application. Lotions are generally of lower viscosity. Diluent A vehicle in a phannaceutical formulation commonly used for making up volume and/or weight (e.g., water, paraffin base). 

Structure Forming Excipient An excipient which participates in the formation of the structural matrix which gives an ointment, cream or gel etc., its semisolid character. Examples are gel fonning polymers, petrolatum, certain colloidal inorganic solids (e.g., bentonite), waxy solids (e.g., cetyl alcohol, stearic acid), and emulsifiers used in creams. 

For liquid (e.g., solution, suspension, elixir) and semisolid (e.g., creams, ointments) dosage forms, a change to or in polymeric materials (e.g., plastic, rubber) of primary packaging components, when the composition of the component as changed has never been used in a CDER-approved product of the same dosage form and same route of administration. For example, a polymeric material that has been used in a CDER-approved topical ointment would not be considered CDER-ap-proved for use with an ophthalmic oinhnent. 

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