Cream / Gel / Lotion / Ointment

Cream / Gel / Lotion / Ointment drug products topically administered via the skin fall into two general categories, those applied for local action and those for systemic effects. Local actions include those at or on the surface of the skin, those that exert their actions on the stratum corneum, and those that modulate the function of the epidermis and/or the dermis. Common products in the former category include creams, gels, ointments, pastes, suspensions, lotions, foams, sprays, aerosols, and solutions. Creams, ointments, and gels generally are referred to as semisolid dosage forms. The most common drug products applied to the skin for systemic effects are referred to as self adhering transdermal drug delivery systems (TDS) or transdermal patches. An ideal topical formulation development can be done by using simple, flexible process. Most topical formulations developed today, however, are complex and, therefore, require tightly controlled processing parameters. Following are five critical process parameters (CPPs) and additional strategies to optimize the contract development (CDMO) of topical dosage forms. Understanding Critical Process Parameters for Topical Product Development Temperature. Processing at the right temperature is critical for successful topical product development. Too much heating during processing can result in chemical degradation. Insufficient heat can lead to batch failures, and excess cooling can result in the precipitation of solubilized ingredients. An example during topical product development (CDMO) is to maintain good temperature control and is the emulsification step of a traditional oil-in-water emulsion. If the temperature of the water phase is much cooler than that of the oil phase, the melted constituents of the oil phase may solidify upon introduction into the aqueous phase and never properly form the emulsion, possibly even resulting in solid matter in the batch. Topical drug development covers the drug that are essential for topical use in local delivery. Superficial drugs provide the local relief. Contract development organizations (CDMO) of topical drug products includes contract development of cream, contract development of lotion, contract development of gels and contract development of ointments. In contract development (CDMO) of lotion and ointments spreading is important as these have thin base and they are applied on the skin to cover greater area. In the contract development (CDMO) of creams the base is thick as these are applied on the skin for longer stay and provide the therapeutic effect. Heating and cooling rates. Heating too slowly can result in poor yields from evaporative loss. Heating too rapidly may burn areas of the batch in contact with the heating surface, which raises the potential for burnt material in the batch. Rapid cooling can result in precipitation/crystallization or increased viscosity. The successful consistency of ointments, for example, depends on proper rates of heating and cooling. Mixing methods and speeds. It is essential to determine the required amount of shear and the optimal mixing methods and speeds. Emulsification typically requires high shear or homogenization to obtain the optimal droplet size and dispersion, while the mixing of a gel may require low shear in order to preserve certain physical characteristics, such as viscosity. Contract development of semi solid dosage forms requires proper mixing speeds must be obtained for each phase at every batch scale. Optimal hydration depends on the amount of shear imparted to initially disperse the polymer into the medium. If the process involves only very low shear mixing, a polymer may never be completely dispersed and hydrated, which may result in an out-of-specification viscosity. Mixing times. Optimizing mixing time requires identifying the minimum time required for ingredients to dissolve and the maximum mixing time before product failure (e.g., when viscosity begins to drop). For polymeric gels, particularly acrylic acid-based types, over-mixing, especially high shear, can break down the polymer's structure. In an emulsion, over-mixing may cause the product to separate prematurely, resulting in a drastic decline in viscosity. Flow rates. Optimizing flow rate involves determining the amount of shear or throughput needed. For example, a water-in-oil emulsion may require a slower addition speed than a traditional, oil-in-water emulsion, and the flow rate must be modified appropriately. Care must be taken for any product using a pump. Overshearing can occur if the formulation is pumped too quickly. For contract development of semisolid or topical products if pumping is too slow, the formulation will experience extra time in an in-line homogenizer, thus also exposing the formulation to additional shear. For topical product development, selection of the right excipients is extremely important. The drug substance may be efficacious, but its interaction with excipients may alter the following: • Its ability to permeate through skin • Its stability through shelf life • Its ability to not metabolize in skin • Its ability to stay dissolved at right concentrations • Its capability to achieve desired release rates For a contract development of topical formulation, an emulsion cream to dissolve the drug up to a certain concentration. The excipients were chosen to optimize the solubility of the drug substance and to prevent oil and water phase separation. However, a change in topical cream formulation development to increase the drug concentration, so it could accommodate the toxicology study requirement, resulted in phase separation due to inadequate emulsifiers. The topical formulation development was redone to optimize the concentration of emulsifiers for development of semi solid dosage forms, as well as the addition of a viscosity-building excipient. A non-homogenous cream could have resulted in erroneous toxicology outcomes. Topical drug development (CDMO) covers the drug that are essential for topical use in local delivery. Superficial drugs provide the local relief. Contract development organizations (CDMO) of topical drug products includes contract development of cream, contract development of lotion, contract development of gels and contract development of ointments. In contract development (CDMO) of lotion and ointments spreading is important as these have thin base and they are applied on the skin to cover greater area. In the contract development (CDMO) of creams the base is thick as these are applied on the skin for longer stay and provide the therapeutic effect. During the early stages of topical product development attention must be given to the permeation enhancers. The bioavailability of the drug in the desired location, ie, epidermis or dermis, must be considered when choosing the right excipient. A solvent that forms a depot of drug concentration may not be ideal for a drug that has site of action in stratum corneum or epidermis. Similarly, during a topical product development project at Contract development, it was discovered during skin permeation studies that the efficacy was best when two permeation enhancers were combined. Early detection of such issues is crucial and helps in selection of right formulation before expensive clinical trials are conducted. While researching excipient compatibility and selection for drug substances/peptides targeted to the dermis, it was discovered that impurities rose in line with increasing pH of 4-7. In skin permeation studies, the release of the peptide was very poor. Homogenates of epidermal and dermal layers of skinat different periods of time showed more stability of the peptide in the dermal layer when compared to the epidermal layer. By explaining the peptide concentration in skin tissues, Contract development of topical preparations found that the peptide was going through degradation with proteolytic enzymes. It is a well-known fact that scale up and certain other process parameters during cream formulation development (CDMO) impact the drug release rate from the formulation. The FDA has developed guidance for the industry to study the impact of Scale Up and Post Approval Changes (SUPAC) for the marketed product. The same principles can be applied to the study of the impact of manufacturing process parameters in choosing the right formulation. The amount of shear produced by the equipment during the contract development of lotion the emulsification can impact the formulation. In a recent project, the formulation for Phase II supplies was being scaled up from Phase I. The viscosity differences led to the need for process optimization to prevent product efficacy differences between two phases of clinical study. In another project, during the contract development of ointment (CDMO) the order of addition of the drug phase made a huge difference in drug stability/compatibility with the formulation excipients. The drug-solvent solution was added to the cream development (CDMO) when it was cooled to 40°C, as opposed to adding it to water phase at 70°C. By contract development of topical formulation the change in the order of addition, the drug stayed in solution without precipitation. If not addressed early and if the right topical cream development process was not chosen, expensive late-stage contract cream development efforts would have been needed to address drug crystallization issues. While performing contract topical product development, optimization studies, to also study the viability of different epidermal and dermal cells allows us to know the dermatological factor compatibility and to find the proper selection of excipients. The analysis of drug/peptide levels in different skin tissue barrier homogenates will allow the researchers to measure the drug/peptide stability and to also find where the drug is targeting. Quality Testing of Topical Formulation General product quality tests are required at vrious steps of topical product development CDMO such as identification, assay, content uniformity (uniformity of dosage units), impurities, pH, water content, microbial limits, antimicrobial preservative content, antioxidant preservative content, and sterility should be performed at various development stages of topical drug products. Several contract development organizations (CDMOs) for topical formulation specialize in developing methods of drug delivery, marketing these products to pharmaceutical companies, and other pharmaceutical companies develop their own systems. Many of these contract development of lotion methods are patented and proprietary. When a drug is administered, the dosage must be carefully calculated so that the body can use the drug, which requires a drug delivery system which allows for precise dosing. Drug delivery systems also need to consider the way in which a drug is metabolized by the body. For example, during contract development of topical formulation some drugs are destroyed in the intestinal tract, which means that they cannot be introduced to the body in this way. Others may be dangerous in large amounts, which means that a time release method should be used to deliver the drug for patient safety. Contract development of topical cream product involve the introduction of a drug to the surface of the body, in a formulation which can be absorbed. Gel contract development (CDMO) are often very easy for patients to use, which makes them appealing. In all cases, the goal of a drug delivery system is to get the right dosage to the right place. Patients tend to prefer methods which are painless and easy, which is why many pharmaceuticals come in the form of topical and enteral methods which can be taken by mouth or applied directly to the skin. In clinical environments, parenteral routes can be more common, especially for controlled substances, because these methods allow for greater control over how and when the drugs are used. Topical drug contract development covers the drug that are essential for topical use in local delivery. Superficial drugs provide the local relief. Contract development organizations (CDMO) of topical drug products includes contract development of cream, contract development of lotion, contract development of gels and contract development of ointments. In contract development (CDMO) of lotion and ointments spreading is important as these have thin base and they are applied on the skin to cover greater area. In the contract development (CDMO) of creams the base is thick as these are applied on the skin for longer stay and provide the therapeutic effect. Contract development organization (CDMO) of topical preparations which are semi solid pharmaceutical products development CDMO, including topical creams, ointments, gels, lotions, non-sterile oral solutions, oral suspensions and nasal sprays. Topical contract development services include cream, lotion, gel, ointment development of new formulations, process optimisation, analytical method development, clinical trial supplies manufacturing, technology transfers and commercial scale-up. Its team has developed many new drug application (NDA), abbreviated new drug application (ANDA), 505(b)2, and over-the-counter (OTC) products within these dosage forms. Types of Topical Formulations Creams Creams are semisolid emulsion systems with opaque appearances as contrasted with translucent ointments. Their consistency and rheologic character depend on whether the emulsion is water in oil or oil-in-water type and/or the nature of the solids in the internal phase. Contract development of creams (CDMO) Oil-in-water emulsions are most useful as water-washable bases where as water-in-oil emulsions are emollient and cleansing. Patients often prefer water in oil cream to an ointment because the cream spreads more readily, less greasy and the evaporating water soothes the inflamed tissue. Contract development of creams, Oil in water creams (vanishing creams) rub into the skin; the continuous phase evaporates and increases the concentration of a water soluble drug in the adhering film. Contract development of cream CDMO, concentration gradient for a drug across the stratum corneum therefore increases, promoting percutaneous absorption. To minimize drug precipitation during the contract development of cream, a formulator may include a nonvolatile, water miscible co-solvent such as propylene glycol. An o/w cream is non-occlusive because it does not deposit a continuous film of water-impervious liquid. Gels Gels are relatively newer class of dosage forms created by entrapment of large amounts of aqueous or hydro-alcoholic liquid in a network of colloidal solid particles, which may consist of inorganic substances such as aluminum salts or organic polymers of natural or synthetic origin. Depending upon the nature of colloidal substances and the liquid in the formulation contract development of gels with a range in appearance from entirely clear to opaque. Most topical gel contract development are prepared with organic polymers such as carbomers which impart an aesthetically pleasing, clear sparkling appearance to the product and are easily washed off the skin with water. Ointments Ointments, in general, are composed of fluid hydrocarbons meshed in a matrix of higher melting solid hydrocarbons. They usually contain a medicament or medicaments dissolved, suspended or emulsified in an ointment base (vehicles). There are greasy in nature. Contract development (CDMO) of ointments requires an ointment base which is a substance or part of an ointment, which serves as carrier or vehicle for the medicament. While selecting a suitable ointment base, the factors such as the action desired, nature of the medicament to be incorporated and the stability of an ointment are to be considered.