Pharmaceutics 1 Lecture 1 & 2 PDF

Pharmaceutics I Dr. Mona Ahmed Shewaiter lecturer of pharmaceutics pharmaceutics department Faculty of pharmacy- Sinai University sinaiuniversity.net Pharmaceutical solutions  Pharmaceutical Solutions What is meant by Dosage form? What is meant by Solution?...

Pharmaceutics I Dr. Mona Ahmed Shewaiter lecturer of pharmaceutics pharmaceutics department Faculty of pharmacy- Sinai University sinaiuniversity.net Pharmaceutical solutions  Pharmaceutical Solutions What is meant by Dosage form? What is meant by Solution?  Pharmaceutical solutions Solution Mixture of two or more components that form a single phase, homogeneous down to the molecular level. Solvent Component that determines the phase of the solution constitutes the largest proportion of the system. Solute The component dispersed throughout the solvent; i.e. dissolved in the solvent. Pharmaceutical solutions Pharmaceutical solutions are liquids in which drug and excipients are dissolved in the chosen solvent system(aqueous or non-aqueous solvents). Advantages of pharmaceutical solutions Easily administered orally to individuals who have difficulty in swallowing such as elderly patients and infants. They are more quickly effective (rapid absorption) than solid dosage forms. Ease of masking bad and bitter taste. They give uniform dose than suspension due to no need for shaking. Disadvantages of pharmaceutical solutions Unsuitable for chemically unstable drugs in water. Unsuitable for poorly soluble drugs. Expensive to ship & bulky to carry. Less stable than solid dosage forms  Drug Solubility In pharmaceutical solutions both the therapeutic agent and the excipients are legally required to be present in solution over the shelf-life of the formulated product.  The dissolution of a therapeutic agent in water involves several key molecular steps: 1. Removal of a molecule of the drug from the solid state. 2. Formation of a cavity within the solvent. 3- Accommodation of the drug molecule into the formed cavity. The aqueous solubility is: 1- high → The drug can be formulated into solution. 2- moderate → Co-solvent is necessary. 3- low → The drug may be formulated in another dosage form (e.g., suspension). Factors affecting drug solubility 1. Melting point of the drug The solubility of chemically related series of a therapeutic agent is inversely related to their melting points. M.P of the drug ---- drug solubility 2. The substituted groups The solubility of a therapeutic agent is directly affected by both the type of chemical substituent groups and the substituent position. Drug has a hydrophilic group such as OH &COOH ---- drug solubility. Drug has a lipophilic group such as methyl & ethyl group ---- drug solubility. 3- PH- dependence pH – pKa = log {(S - So) / So )} For acids pH - pKa = log {So / (S - So) } For bases Where; S The solubility of the drug So The solubility of the unionized form of the drug The solubility of acidic compounds increases as pH of solution increases(above the pKa). The solubility of basic compounds increases as pH of solution decreases (below the pKa).  Formulation methods to enhance drug solubility The information described below may be employed to optimize the formulation of pharmaceutical solutions, remembering that the prerequisite for pharmaceutical solutions is the exclusive presence of dissolved therapeutic agent. 1. Chemical Modification e.g. Drug salt. 2. Optimization of PH of the formulation. 3. Co-solvents. 4. SAA and Complexation.  Excipients used in pharmaceutical solutions 1. Must be physiologically inert. 2. Facilitate administration of the dosage form. 3. Increase drug chemical & physical stability.  Types of excipients used in pharmaceutical solutions 1. The vehicle 2. Co-solvents 3. Buffers 4. Sweetening Agents 5. Viscosity enhancing agents 6. Antioxidants 7. Preservatives 8. Flavors 9. Colorants  1- The vehicle What is the most commonly used vehicle?  1- The vehicle Types of water: 1. Potable water (tap water). 2. Mineral water. 3. Purified water. 4. Water for injection (WFI). 4.1. Sterile WFI. 4.2. Bacteriostatic WFI.  1- The vehicle The preferred is purified water, due to Example low cost and low toxicity  purified water is: a- Prepared from tap water by Notes b.1. Distillation, b.2. Ion exchange b.3. Reverse osmosis method. 1- The vehicle 1- The vehicle 1- The vehicle https://www.youtube.com/watch?v=4RDA_B_dRQ0  1- The vehicle Notes a- Not used for parenteral. b- The solid residue is less than 1 mg per 100 ml of evaporated sample  1- The vehicle Alcohol USP: ethyl alcohol, ethanol, C2H5OH Next to water, alcohol is the most useful solvent in pharmacy. It is used as a primary solvent for many organic compounds. Together with water, it forms a hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble substances. Well recognized as a solvent and excipient in the formulation of oral pharmaceutical products.  1- The vehicle Alcohol USP: ethyl alcohol: Alcohol is preferred due to: Miscibility with water. Ability to dissolve many water-insoluble ingredients, including drugs, flavorants, and antimicrobial preservatives. Types of Ethyl alcohol:  Alcohol USP:(94.9% to 96.0% C2H5OH by volume (i.e., v/v).  Dehydrated Alcohol (absolute alcohol) contains not less than 99.5% C2H5OH by volume and is used when an essentially water-free alcohol is desired.  1- The vehicle Functions of Ethyl alcohol:  Solvent.  Co-solvent.  Preservative. Alcohol USP: ethyl alcohol, ethanol, C2H5OH Despite its pharmaceutical advantages, concern has been expressed over the undesired pharmacologic and potential toxic effects of alcohol, particularly by children.  1- The vehicle OTC oral products: for children under 6 years, the recommended limit is 0.5%. for children 6 to 12 years, the recommended limit is 5%. for children over 12 years and for adults, the recommended limit is 10%.  1- The vehicle Glycerin USP (Glycerol): Clear odorless liquid with a sweet taste. Miscible with both water and alcohol. Has preservative qualities and is often used as a stabilizer It is used in many internal preparations. Used as an auxiliary solvent in conjunction with water or alcohol. Because of its viscosity, solutes are slowly soluble in it unless it is rendered less viscous by heating.  1- The vehicle Propylene Glycol, USP, CH3CH(OH)CH2OH Viscous liquid, miscible with water and alcohol. Has a wide range of applications. Frequently substituted for glycerin in modern pharmaceutical formulations.  2- Co-solvents: Used to: Used to increase the drug solubility. Example a-Alcohols: 1. Ethyl Alcohol. 2. Glycerol. 3. Propylene glycol. 4. Poly(ethylene glycol) (PEG)  2- Co-solvents: 4. Poly(ethylene glycol) (PEG) is a polymer composed of repeating units of the monomer ethylene oxide (in parenthesis). Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-solvents in pharmaceutical solutions.  2- Co-solvents: Used to: Used to increase the drug solubility Example b- Surface active agents: These are chemicals having both hydrophilic & hydrophobic groups. Its action occur at CMC and used for solubilization of poorly soluble drugs resulting homogenous clear solutions.  2- Co-solvents: c- Complexation: interaction of poorly soluble drugs with organic molecule such as hydrophilic polymer to form soluble intermolecular complex which dissociate after administration. Drug + hydrophilic organic molecule → soluble complex (dissociate after administration)  3- Buffers: Used to control pH → to maintain drug solubility & stability. The concentration (and hence buffer capacity) of buffer salts employed in the formulation of oral solutions should be selected to offer sufficient control of the pH of the formulation  3- Buffers: Acetate buffer (acetic acid /sodium acetate) 1-2% Citrate buffer (citric acid /sodium citrate) 1-5% Phosphate buffer (sodium Phosphate + disodium phosphate) 0.8-2% The buffer system used in solution formulations should not adversely affect the solubility of the therapeutic agent, e.g. the solubility of drugs may be affected in the presence of phosphate salts.  4- Sweetening Agents Used To increase palatability of the therapeutic agent Examples: sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and aspartame. N.B. The use of sugars in oral formulations for children and patients with diabetes mellitus is to be avoided.  5- Viscosity enhancing agents: Used to ensure accurate measurement of volume to be administered. Furthermore, increasing the viscosity of some formulations may increase the palatability. Certain liquid formulations do not require the specific addition of viscosity-enhancing agents, e.g. syrups, due to their inherent viscosity.  5- Viscosity enhancing agents: a- Non-ionic polymers: as cellulose derivatives (MC (methyl cellulose), HEC (Hydroxyethyl cellulose), HPC (Hydroxypropyl cellulose) and PVP (Polyvinylpyrrolidone)). b- Ionic polymers: as sodium carboxy methyl cellulose (sodium CMC) and sodium alginate (anionic).  6- Antioxidants They are used to enhance the stability of drug that are susceptible to chemical degradation by oxidation. They are molecules which exhibit higher oxidation potential than drug itself. The antioxidants in aqueous solution is oxidized (hence it is degraded) in preference to the drug and prevent drug oxidation Antioxidants are employed in low concentrations ( 0.2% w/w)  6- Antioxidants 1- For aqueous formulations: ascorbic acid, sod. formaldehyde sulfoxylate, sodium sulfite & sod. metabisulfite. 2- For oily-based solutions: butylated hydroxyl toluene (BHT) butylated hydroxyl anisole (BHA) & propyl gallate. Antioxidants may be used in conjunction with chelating agents e.g. ethylenediamine tetraacetic acid (EDTA), citric acid, that form complexes with heavy-metal ions, ions that are normally involved in oxidative degradation of therapeutic agents.  7- Preservatives: Used to control the microbial activity in the formulation Possess a broad-spectrum antimicrobial activity. (gm–ve, gm+ve bacteria & fungi) Chemically and physically stable over the shelf life period of product. Have low toxicity. Alcohols: Ethanol as a preservative (greater than 10%). Propylene glycol (15 to 30%). Other alcohols used in lower concentrations (about 1%), include chlorobutanol and phenylethyl alcohol.  7- Preservatives: Acids: Benzoic acid has a low solubility in water. Effective Conc. (from 0.1 to 0.5%). Sorbic acid has a low solubility in water. Effective Conc. (from 0.05 to 2%). Esters: Alkyl esters of p-hydroxybenzoic acid. Effective conc (0.001- 0.2 %) Called Parabens.  7- Preservatives: Esters: Parabens include the methyl, ethyl, propyl and butyl derivatives. Used widely in pharmaceutical products. Frequently, two esters are used in combination in the same preparation. The most widely used preservatives are mixture of Methyl parahydroxybezoate in 0.2% and Propyl parahydroxybenzoate in 0.02%. They are suitable for both external and internal use. The combination of the methyl and propyl parahydroxy benzoates (in a ratio of 9:1) enhances the antimicrobial spectrum.  Factors affecting the preservative efficiency in oral solutions: The activity of a preservative is dependent on the correct form of the preservative being available in the formulation at the required concentration to inhibit microbial growth Factors that directly affect the efficacy preservatives in oral solutions include: 1) pH of the formulation 2) The presence of micelles. 3) The presence of hydrophilic polymers.  8- Flavors Used to To mask the taste of the drug or the formulation Example The four basic taste sensations are: salty, sweet, bitter and sour  8- Flavors  Vanilla, wintergreen mint flavors to mask salty taste  Vanilla, fruit and berry to mask a sweet taste.  Anise, cherry flavors to mask a bitter taste.  Citrus, raspberry flavors to mask sour taste  Usually, a combination of flavors is used to achieve the optimal taste-masking property.  9- Colorants: Used to To impart the preferred color to the formulation. Example The selected color should match the flavor of the formulation.eg: green with mint, red with strawberry flavor. THANK YOU