Pharmaceutics I Lecture 6 PDF

PHTC 312 Pharmaceutics I PHARMACEUTICAL SUSPENSIONS Lecture 6 Prof. Samar Mansour Professor of Pharmaceutical Technology Winter 2024  Comptencies Comprehend the physicochemical principles controlling the formulation and per...

PHTC 312 Pharmaceutics I PHARMACEUTICAL SUSPENSIONS Lecture 6 Prof. Samar Mansour Professor of Pharmaceutical Technology Winter 2024  Comptencies Comprehend the physicochemical principles controlling the formulation and performance of suspensions Discuss the role of pharmaceutical excipients with regards to formulation of suspensions Formulate independently the pharmaceutical suspensions Compare between different types of pharmaceutical dosage forms Justify some pharmaceutical techniques and excipients used for suspensions formulation Analyze, retrieve & evaluate information from different sources specific to pharmaceutical dosage forms.  Liquid Dosage Forms Solutions One homogenous phase, prepared by dissolving one or more solutes in a solvent Disperse systems (Suspensions) A dispersion system where solid particles are dispersed in liquid phase≥1 µm. Disperse systems (Colloids) A dispersion system where solid particles are dispersed in liquid phase 1 µm. Disperse systems (Emulsions) A dispersion system consisting of two immiscible liquids (Cloudy appearance) Solution and Disperse systems  Disperse Systems Disperse system compose of at least two phases : a. Disperse or internal phase b. Continuous or external phase (dispersion medium or Vehicle ) Disperse Systems: I. Suspensions II. Colloids III. Emulsions.  Outline of Pharmaceutical Suspensions lectures: Definition Types of suspensions Properties of well formulated suspensions Reasons for preparing pharmaceutical suspensions Preformulation Phase Formulation of suspensions Formulation additives Rheology of suspensions Methods for preparation Stability Testing of pharmaceutical suspensions  Disperse Systems COARSE SUSPENSIONS A solid in liquid dispersion in which the particles are above colloidal size (1 um). Disperse System Dispersion Dispersed medium phase Aqueous insoluble oily liquid solid  Coarse Suspensions It is a dispersion of finely divided insoluble solid particles (disperse phase) in a fluid (dispersion medium) Dispersion medium: aqueous, oily liquid Dispersed phase: insoluble solid Solid exhibits minimum degree of solubility  Types of Pharmaceutical Suspensions 1- According to dispersion medium: * Aqueous suspensions * Oily suspensions 2- According to the stability of the drug: * Ready to use Suspensions ( for stable drugs) or *Reconstituted Suspensions “powder for reconstitution” ( For non stable drugs) 3- According to formulation: Flocculated or Deflocculated 4- According to uses and route of administration Oral, Parenteral, Topical preparations, Ocular eye drops Physical properties of a well-formulated suspension 1. It must remain homogenous for the period between shaking container and removing the required dose. 2. The sediment produced on storage must be easily resuspended by the use of moderate agitation. 3. The viscosity must not be so high that removal of the product from the container is difficult. 4. The suspended particles should be uniformly sized to give a smooth product free from a gritty texture. 5. Resistance to microbial contamination.  Pharmaceutical Applications of Suspensions Reasons for preparing suspensions 1- People having difficulty in swallowing solid dosage forms If the drug is insoluble (a suspension is required). 2- Drugs with poor solubility 3- Bad taste drugs: The tastes drugs are more noticeable if in solution than if in an insoluble form. Paracetamol suspension is more palatable than solution “Pediatric Paracetamol Elixir”  Pharmaceutical Applications of Suspensions 4- Easily degraded drugs in the presence of water: (stability reason) (suspensions are more stable than solutions) A- It may be possible to synthesize an insoluble derivative and formulate it as a suspension E.g.: (oxytetracycline HCl aqueous solution would hydrolyze rapidly While: insoluble calcium salt of oxytetracycline in aqueous vehicle (stable) B- Formulate the drug as Reconstituted suspension: decrease the contact between solid drug particles and dispersion medium Pharmaceutical Applications of Suspensions 5- Materials which should be present in the GIT in a finely divided form and their formulation, as suspensions will provide the desired high surface area. a- Adsorption of toxins in case of diarrhea (kaolin- pectin) Pharmaceutical Applications of Suspensions 5- Materials which should be present in the GIT in a finely divided form and their formulation, as suspensions will provide the desired high surface area. b- Neutralize excess acidity in stomach (antacids) (Aluminum/ magnesium hydroxide) ( magnesium carbonate and magnesium trisilicate) Pharmaceutical Applications of Suspensions 6- Topical application: * (Lotions) Fluid (Calamine Lotion BP). Calcipotriene-Betamethasone 0.005 %- 0.064 % Topical Suspension Antipsoriatics treat: psoriasis of the scalp and body  Pharmaceutical Applications of Suspensions 7- Suspensions formulated for parenteral administration for Two reasons for parenteral: A- prolongation of action of the drug or B- better stability IM parenteral suspension IV parenteral suspension ?????? ( restricted)  Pharmaceutical Applications of Suspensions 7- Suspensions formulated for parenteral administration for prolongation of action of the drug: To control the rate of absorption of the drug and duration of activity (Depot, reservoir, Long acting) e.g.: Benzathine Penicillin A- Varying particle size: duration of activity (controlled) B- Use Different vehicles to suspend the drug: *Aqueous vehicle diffusion of the product will occur along muscle fibers after injection. * Use Fixed oils such as arachis or sesame oils In order to prolong activity. (Oily Suspension more prolonged activity than Aqueous Suspension)  Pharmaceutical Applications of Suspensions 8- Aerosol suspensions: suspensions of the active agent in a mixture of propellants. Topical- inhalation  Preformulation of suspensions I- Selection of the suitable particle size. II- Control the Particle size to avoid the Change in the particle size distribution. 1- It is necessary to ensure that the drug particle size is optimum, if greater than about 10 µm diameter, will: a- impart gritty texture to the product. b-cause irritation if injected or instilled into the eyes. c- block hypodermic needle diameter 2- Use a particular particle size range (every batch) to control the rate of solubility of drug and the bioavailability. 3- It is advantageous to use a suspended drug of narrow size range  Preformulation of suspensions 4- Use the stable polymorphic form of the drug to prevent any change in particle size Different polymorphic forms of a drug may exhibit different solubilities. Conversion of the metastable form in solution (soluble) to the less soluble stable state and its subsequent precipitation will lead to changes in particle size. Metastable Precipitation Stable Soluble changes in particle Less Soluble form form size distribution.  Preformulation of suspensions 5- Prevent temperature fluctuation and Crystal Growth **on storage: Crystal growth can occurs particularly if temperature fluctuation occurs. because the solubility of the drug increase as the temperature rises but on cooling the drug will crystallize out. (Change in the particle size distribution)  Crystal growth and change in particle size distribution can be controlled by the following procedures and techniques: 1- Selection of the suitable particle size. (bet. 1-10 microns) 2- Selection of stable crystalline drug form that exhibits lower solubility “Not the metastable form”. 3- increase the viscosity of the vehicle to retard dissolution and crystal growth. 4- Prevent the temperature fluctuation during product storage. 5- Use particles with narrow size range YOU