Medicines Design & Manufacture - Pharmaceutical Solutions

Define a pharmaceutical solution in terms of the disperse phase (solute) and dispersion medium (solvent).
Differentiate solutions from suspensions and emulsions.
Provide examples of pharmaceutical solutions.
Demonstrate knowledge of the common classes of polymers used as viscosity modifiers in pharmaceutical solutions.
Understand the importance of rheology with respect to the design of medicines.

A solution is defined as:
- Mixture of components: Two or more components form a single phase that is homogeneous down to the molecular level (M.E. Aulton, 2007).
- Phases: Composed of solute (disperse phase) that is dissolved in the solvent (dispersion medium).
- Types of components: Both solute and solvent can be solid, liquid, or gas (e.g., solid-in-liquid, liquid-in-solid, gas-in-liquid).
- Focus in this course: Primarily solid-in-liquid solutions.

Solution: A solid dissolved in a solvent.
Suspension: A solid dispersed in a liquid.
Emulsion: A liquid dispersed in a liquid.
Miscibility vs. Solubility: When discussing the mixing of liquids or gases, use the term miscibility instead of solubility.

Syrup: A liquid medicine containing a sugar solution for flavoring or preservation.
Elixir: A medicinal liquid mixed with syrup, glycerin, or alcohol to mask unpleasant tastes.
Linctus: A syrupy preparation to relieve coughs or sore throats.
Mixture: Can refer to either a solution or a suspension.
Drops: May be a solution or suspension used for mouth, tongue, eyes, or ears applications.

Uniformity: Drug is uniformly distributed throughout the solution.
Accurate Dosing: Provides a uniform dose when volume is measured.
Quick Absorption: No delay in absorption as the drug is already in solution.
Ease of Swallowing: Especially for oral solutions.

Stability: Generally less stable than solid dosage forms.
Taste: Unpleasant flavors can be difficult to mask.
Portability: Bulky, requiring accurate measuring equipment (5 mL spoon or syringe).

Syrup BP: Composed of 66.7% w/v sucrose (water to 100%). High concentration necessary for stability, which prevents microbial growth.
Aqueous Solutions:
- Nasal Solutions: Mainly isotonic saline (0.9% w/v); used for decongestion or local steroid administration.
- Eye Drops: Often isotonic saline that may contain antibiotics (e.g., chloramphenicol).
- Ear Drops: Similar to eye drops, may contain antibiotics or steroids.
- Oropharynx Solutions: Saline, steroids, antiseptic mouthwashes used for mouth and throat treatment.
- Enemas: Administered either as oily or aqueous solutions.

Polymers are used to enhance the viscosity of pharmaceutical solutions, affecting flow properties and stability.

Natural Polymers:
- Polysaccharides: Example sources include plant cells (e.g., starch, cellulose, alginate) and animal sources (e.g., chitin, gelatin).
- Proteins: Collagen, albumin, etc.
Semi-synthetic Polymers:
- Cellulose Ethers:
  - Methylcellulose (MC)
  - Hydroxypropylmethylcellulose (HPMC)
  - Carboxymethylcellulose sodium (CMC)
Synthetic Polymers:
- Poly(acrylic acid) (Carbomer)
- Poly(vinyl pyrrolidone) (PVP)
- Poly(ethylene glycol) (PEG)

Dynamic Viscosities at 20°C (293 K):
- Water: 1.0 mPa.s
- Chloroform: 0.6 mPa.s
- Ethanol: 1.2 mPa.s
- Glycerol: 1000 mPa.s
- Castor oil: 400 mPa.s
Common Rates of Shear:
- Pouring: 50 s⁻¹
- Spreading lotion: 500 s⁻¹
- Hypodermic needle injection: 5,000 s⁻¹
- Processing in a colloid mill: Up to 100,000 s⁻¹.

Newtonian: Constant viscosity regardless of shear rate (e.g., water, oils).
Plastic: Requires a threshold stress to start flowing (e.g., ointments).
Pseudoplastic: Viscosity decreases with increasing shear rate (e.g., certain polymer solutions).
Dilatant: Viscosity increases with shear rate, rare in pharmaceuticals (e.g., suspensions with high solid content).