Pharmaceutical, Cosmetic and Personal Care Formulations

Tharwat F. Tadros

• Publisher: De Gruyter
• Year: 2018
• ISBN:
  9783110587593
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

Volume 3 of Formulation Science and Technology is a survey of the applications of formulations in a variety of fields, based on the theories presented in Volumes 1 and 2. It offers in-depth explanations and a wealth of real-world examples for research scientists, universities, and industry practitioners in the fields of Pharmaceuticals, Cosmetics and Personal Care.

Part I:Pharmaceutical formulations

1Pharmaceutical suspensions

1.1Introduction

The suspension is often selected as a pharmaceutical dosage form when the drug is insoluble in water and aqueous fluids at the dosage required for administration. The large surface area of the dispersed drug ensures a high degree of availability for absorption. Unlike tablets or capsules, the dissolution of drug particles in suspension and subsequent in vivo absorption commence upon dilution in the gastrointestinal fluids. Finely divided particles dissolve at a greater rate and have relatively higher solubility when compared with similar macroparticles (Chapter 10 of Vol. 1).

Several types of pharmaceutical suspensions are formulated, of which orally administered suspensions, parenteral suspensions (injectable suspensions) and externally applied suspensions (sometimes referred to as lotions) and are probably the most applicable [1, 2]. The solid content of an oral suspension may vary considerably. For example, antibiotic suspensions may contain 125 to 500 mg active solid material per 5ml (teaspoon) dose, while the drop concentrate may provide the same amount of insoluble drug in a 1 or 2 ml dose. Antacids and radiopaque suspensions also contain relatively high amounts of suspended material for oral administration. The vehicle is either syrup, sorbitol solution or gum thickened water with added artificial sweeteners. In case of limited “shelf life” (limited chemical stability of the drug), the dosage form may be prepared as a dry granule or powder mixture that is suspended in water prior to use.

Parenteral suspensions are ideal dosage forms for prolonged therapy. Administration of a drug as an aqueous or oil suspension into subcutaneous or muscular tissue results in the formation of a depot at the injection site. The depot acts as a drug reservoir, slowly releasing the drug molecules continuously at a rate related to both the intrinsic aqueous solubility of the insoluble drug form and the type of the suspending vehicle used, either aqueous or oil for the purpose of maintaining systemic absorption of drug from the injection site [2]. The solid content of parenteral suspensions is usually between 0.5 and 5%, with the exception of penicillin which may exceed 20 %. These sterile suspensions are used for intramuscular, intradermal intralesional, intraarticular or subcutaneous administration. The viscosity of the parenteral suspension should be low enough to facilitate injection. Common vehicles (which must be safe for use) for parenteral suspensions include preserved sodium chloride injection or a parenterally acceptable vegetable oil. Ophthalmic suspensions that are applied to the eye must also be prepared in a sterile manner. The vehicles employed are essentially isotonic and aqueous in composition.

Topical suspensions, referred to as “shake lotions”, are commonly applied as dermatological preparations and usually contain high concentrations of disperse phase (> 20 %). These suspensions, which have the same consistency as cosmetic lotions, exhibit hindered settling rates (Chapter 13 of Vol. 1). The vehicle of the suspension may consist of a dilute oil-in-water emulsion or a clay suspension to prevent particle settling.

Most particles in drug suspensions are hydrophobic in nature and they require a wetting agent to aid dispersion in aqueous media (see below). However, particles of antacid suspensions, e.g. containing clays, aluminium hydroxide, magnesium hydroxide, etc., are hydrophilic in nature and they generally do not require a wetting agent for dispersion in aqueous media.

1.2Oral suspensions

Aqueous drug suspensions are often very effective pharmacologically and they are frequently less complicated to formulate than other dosage forms [3]. As mentioned in the introduction, drugs formulated as suspensions are more bioavailable than comparable tablets or capsules. This is due to the smaller particle size (higher surface area) of the drug that enhances the rate of dissolution and solubility of the drug. In addition, possible modification of the drug’s bioavailability can be an advantage of this dosage form. A delayed drug absorption (due to the increased viscosity of the vehicle) would result in a prolonged clinically useful plasma concentration of the drug.

Several requirements are necessary for oral suspension formulations [3]:

1. The dispersed particles should be small and uniform and they should not show fast settling. If this occurs, the particles should be easily redispersed by gentle shaking.
2. The viscosity of the system should be sufficiently low for easy pouring and redispersion. The redispersal should produce a uniform dose for administration.
3. The suspension should be chemically and physically stable for the shelf life of the product.
4. The final formulations should have a pleasant taste, colour and odour.

For formulation of an oral suspension, it is necessary to have an adequate wetting agent, dispersing agent (protective colloid) and a suspending agent (rheology modifier) to reduce or prevent particle settling (Chapters 13 and 14 of Vol. 1). Other ingredients in the suspe...