Pharmaceuticals: Semi-Solids Manufacturing
Semi-solids, shown below, can be broken down into various types including creams, gels, and ointments. The manufacturing process for these semi-solids are very similar, therefore this section will cover semi-solids as a whole and mention details about each subgroup as they are relevant. The Active Pharmaceutical Ingredient, or API, gives the semi-solid its medicinal attributes. The API and inactive ingredients are first mixed, usually at elevated temperatures. Once properly mixed, the semi-solid is cooled to a working temperature and packaged. Depending on the product, some semi-solids will then undergo sterilization. After packaging, and sterilization if necessary, the semi-solid is ready for distribution.
This module describes production equipment relevant to these process steps. The Quality Control module describes additional equipment used to monitor quality parameters during this process.
The first step in developing a semi-solid is to mix active and inactive ingredients together, using high shear mixers at an elevated temperature to force the ingredients to mix. Many ingredients in semi-solids generally do not mix well under normal conditions, for example, mixing oils and water to make creams and ointments or suspending API's in a gel matrix. Elevated temperatures are used to reduce the viscosity of the semi-solid while in the working phase to ensure the mixers can properly handle the ingredients.
Occasionally, the mixing process is a multi-step process. Depending on the formulation for the semi-solid, premix vessels are often used to mix certain ingredients first, before being transferred to a final mixing vessel. Commonly used mixers include ribbon mixers and mullers.
Ribbon mixers are used for their ability to scrape the outside wall of the mixer. When dealing with semi-solids that have a high viscosity, the ribbon mixer can help force the mixture off of the walls and induce mixing.
(Copyright H.C. Davis Sons Manufacturing Co., Inc., Bonner Springs, KS)
In general mixers need to be able to handle liquid and semi-solid phases. Therefore, are often used for their ability to handle a mixture composed of two phases. The rollers on a muller induce high shear mixing, which is ideal for semi-solid manufacturing.
Once the semi-solid is properly mixed, the product is ready for packaging. In order to package a semi-solid, the product is first set to a “working” temperature. This is the lowest possible temperature that can be achieved while still maintaining a low viscosity which will allow for packaging. If the viscosity of the semi-solid is too high, it will be very difficult to force the semi-solid into the correct packaging. However, if the temperature is too high, thermal degradation will often occur and spoil the product.
Additionally, the type of packaging container must account for several factors, including corrosion and permeation. If the wrong type of container is used, it could inadvertently spoil the product. Generally aluminum or polyethylene tubes are used as containers.
For some semi-solids, packaging is the last step in semi-solid manufacturing, and the product is ready for distribution. However, if the product needs to be a sterile a sterilization step must follow.
The last step in semi-solid manufacturing for some semi-solids is sterilization. Semi-solids that require sterilization are generally, meant to be used internally, such as burn creams or lip ointments.
The most common way to sterilize a product is to subject the packaged product to a bombardment of gamma radiation for a set period of time. The gamma rays effectively eliminate any microbes that could be present in the semi-solid. Once the product is properly sterilized, it is ready for distribution.
A second and less common way to produce sterile products is to have the entire semi-solid manufacturing process run under clean room conditions. This means that all workers and machinery operate in a certified clean room that has little or no microbes present. Subsequently, semi-solids manufactured in a clean room do not require gamma radiation after packaging. However, due to the high cost of building a certified clean room, this method is not widely used.
After sterilization, semi-solid pharmaceuticals are tested against product specifications. The Quality Control module describes equipment relevant to this testing process.
H.C. Davis Sons Manufacturing Co., Inc. , Bonner Springs, KS
Niazi, S.K., Handbook of Pharmaceutical Manufacturing Formulations Semisolid Products Volume 4. United States of America: CRC Press, 2004. Print.
Wang, H.Y, University of Michigan, personal communications, 2016.
Yuan, Y., Pfizer Inc., personal communications, 2016.