1. Define the following terms: a.) Pharmaceutics – It is the study on the formulation, manufacture, stability, and effectiveness of pharmaceutical dosage forms. b.) Pharmaceutics ingredients or excipients – It is the selective use of these non-medicinal agents. c.) Master formula – It is the formulation that best meets the goals of the product. d.) Stability – Extent a product retains within specified limits and through its period of storage and use e.) Dissolution rate – It is the time for the drug to dissolve in the fluids at the absorption site (ratelimiting step in absorption). f.) Expiration date – It limits the time during which the product may be dispensed by the pharmacist or used by the patient. g.) Partition coefficient – It is the selection of appropriate extraction solvents, drug stability, use of salting-out additives and environmental concerns.
2. Give the principal reason for the need of dosage forms and some dosage forms for specific reasons.
To protect the drug substance from the destructive influences of atmospheric oxygen or humidity. (Coated tablets) To protect the drug substance from the destructive influence of gastric acid after oral administration. (Enteric-coated) To conceal the bitter, salty or offensive taste or odor of a drug substance. (Capsules, Flavored syrups) To conceal the bitter, salty or offensive taste or odor of a drug substance. (Capsules, Flavored syrups) To provide clear liquid dosage forms of substances. (Syrups, Solutions) To provide rate-controlled drug action. (Controlled-release tablets) To provide optimal drug action from topical administration sites. (Ointments,Creams, Transdermal patches) To provide for insertion of a drug into one of the body’s orifices (Suppositories) To provide placement of drugs directly in the bloodstream or body tissues (Injections)
To provide for optimal drug action through inhalation therapy (Inhalants, Inhalation aerosols)
3. Before medicinal substance is formulated, what factors related to illness must be considered?
Following are the factors that must be considered before medicinal substance is formulated: Therapeutic matters (nature of the illness) Manner it is treated (locally or through systemic action) Age and anticipated condition of the patient.
4. Give 3 ways by which a liquid drug could be given in solid sol id form to be given orally. Liquid substance:
Sealed in soft gelatine capsule Developed into a solid ester or salt form suitable for tablets or drug capsules Mixed with a solid or melted semisolid material melted mixture is poured into hard gelatine capsules to harden & capsules sealed
5. Give the importance of the ff. to the drug substance/product: a.) Microscopic examination of the raw drugs indication of: particle size and size range of the raw material along with the crystal structure. information in formulation processing attributable to changes in particle or crystal characteristics of the drug. b.) Melting point depression It determines the: purity of the substance and compatibility of various subs before inclusion in the dosage form - Pure substance : sharp melting point - Impure substance : depressed melting point c.) Phase rule It is where phase diagrams are constructed to determine the existence & extent of the presence of solid and liquid phases in binary, ternary & other mixtures.
d.) Rate reaction It is the description of the drug concentration with respect to time. e.) Extent of dissociation/ionization It is the extent of ionization of drug - strong effect on formulation & pharmacokinetic parameters of the drug. It is determined by potentiometric titration. f.) Fick’s Law (Law of Diffusion) It describes the relationship of diffusion & dissolution of the active drug in the dosage form & when administered in the body. - 1st law Relates to a steady state flow - 2nd law Relates to a change in conc. of drug with time, at any distance, or a nonsteady state of flow
6. Give the methods of determining the following: a.) Dissolution rate – The time it takes for the drug to dissolve in the fluids at the absorption site, is the rate-limiting step in absorption. Dissolution rates of chemical compounds are determined by 2 methods: 1. Constant-surface Constant-su rface method – which provides the intrinsic dissolution rate of the agent 2. Particulate dissolution – in which a suspension of the agent is added to a fixed amount of solvent without exact control of surface area. b.) Drug’s solubility – It is usually determine by the equilibrium solubility method, by which an excess of the drug is placed in a solvent and shaken at a constant temperature over long period until equilibrium is obtained. c.) Membrane permeability – In order to produce a biologic response, the drug molecule must first cross a biologic membrane. The biologic membrane acts as a lipid barrier to most drugs and permits the absorption of lipid-soluble substances by passive diffusion, while lipid insoluble substances can diffuse across the barrier only with considerable difficulty if at all.
d.) Molecule’s lipophilic lipophilic character It is measured by the oil-water coefficient. e.) pKa It is is determined by potentiometric titration. For the pharmacists, it is important to predict the precipitation in admixtures and to calculate the solubility of drugs at certain pH values. f.) Shelf-life determination It has to be estimated based on assay results of the drug characteristic from a stability study usually conducted during the process of drug development. 7. How will these factors affect solubility of the drug’s substance? (NOT SURE OF THE ANSWER) If a drug is formulated to liquid product, adjustment of pH of solvent where drug is dissolved to adjust solubility. Further, chemical analysis of the drug content in solution is performed to determine degree of solubility. 8. Give ways by which dissolution rate is increased. a.) The dissolution rate of drugs may be increased by decreasing the drug’s particle size. b.) It may also be increased by increasing its solubility in diffusion layer. c.) The most effective means of obtaining higher dissolution rates is to use a highly water soluble salt of the parent substance.
9. Enumerate and explain the 5 types of stability. a.) Physical Stability means that the original physical properties like appearance, palatability, viscosity, uniformity of color maintained until expiry date. b.) Chemical Stability means that the active ingredient retains its chemical integrity and labeled potency are retained over extended period of time. c.) Microbial Stability means that the activity or resistance to microbial growth should still according to specified requirements. Preservatives must be added to prevent the growth of microorganism. d.) Therapeutic Stability means that the therapeutic therapeutic effect maintained until expiry date. e.) Toxicological Stability means when no significant increase in toxicity has occurred.
10. What are the 5 processes by which a drug could be degraded? a.) Polymerization It is a reaction between two or more identical molecules with resultant formation of new & generally larger molecule (Ex. formaldehyde) b.) Decarboxylation The decomposition of Carboxylic of Carboxylic acid (R-COOH) and release of carbon dioxide (CO2) c.) Deamination The removal of nitrogen containing group from organic amine (Ex. Insulin) d.) Hydrolysis The process in which drug molecule interact with water molecules to yield breakdown products of different chemical constitution. (Ex. Aspirin) e.) Oxidation A destructive process occurring in pharmaceutical. Chemically, it involved the change in the number of electrons from an atom or molecule.
11. Give ways to prevent decomposition of the drug substance by: a.) Oxidation Light is catalyst to oxidation reactions. Thus, preparation should be packaged in light resistant or opaque containers. containers. b.) Hydrolysis Water should be reduced or eliminated from the system. For water-liable drugs, waterproof protective coating is applied in the tablet. In liquid formulation, water is replaced by substitute liquids.
12. How drug instability be detected? Drug instability can be detected if there are changes in physical appearance, color, odor, taste or texture of the formulation.
13. Differentiate long term stability studies with accelerated stability studies according to: Long term stability studies Product is subjected to different climatic zones (temperature & humidity) nationally and internationally
Duration
12 months minimum
Temperature
Conducted at 25 o C +/- 2oC and at
Humidity
a relative humidity of 60% +/- 5%
Accelerated stability studies Use of exaggerated conditions of temperature, humidity, light and others
6 months study 40 o C
75% relative humidity
14. What are the FDA guidelines on stability for extemporaneous compounding?
Nonaqueous liquids & solid formulations (Source of active ingredient)’s Not later than 25% of the time remaining until the product’s expiration date or 6 months, whichever is earlier Nonaqueous liquids & solid formulations in w/c USP or NF substance (Source of ing) Beyond-use not later than 14 days in storage at cold temperatures Other formulations beyond-use date of the intended duration of therapy or 30 days whichever is earlier
15. Tabulate some pharmaceutic ingredients, their uses and common examples.
Pharmaceutic Ingredients
Uses
Common Examples
Solvents
Used to dissolve the drug substance
alcohol
Flavors and sweeteners
Used to make the product more palatable
aspartame
Colorants
Added to enhance appeal
dyes
Preservatives
May be added to prevent microbial growth
Ophthalmic and injectable preparations
16. What is Delaney Clause Delaney clauses states that no new food additives may be used if animal studies/appropriate studies/appropriate tests tests showed that that it caused cancer. cancer.
17. Give examples of sweetening agents and their advantages and disadvantages. Sweetening Agents
Stevia
(Stevia rebaudiana Bertoni)
Advantages
helpful aid in weight loss due to the fact that it contains no sugar, no calories and has been shown to reduce craving for sweets and fatty foods.
Disadvantages it leaves some unpleasant tastes such as a bitter taste. In other words, it is undesirable for a sweetening to contain large amounts of Stevioside.
Saccharin
metabolized and excreted by the kidneys virtually unchanged
may cause sulfa allergies and has possible carcinogenic properties when consumed in very large amounts
Aspartame
breaks down in the body into three basic components: the amino acids phenylalanine and
the use of aspartame by persons with phenylketonuria (PKU) is discourages,
aspartic acid, and methanol
18.
and diet foods and drinks must bear appropriate label warning
What is the origin of synthetic colorant?
The synthetic coloring agent comes mostly from coal tar (pix carbonis) black, viscid liquid which is a byproduct in the destructive distillation of coal. Most pharmaceutical colorants are synthetic origin; few are naturally occurring principles obtained from mineral, plants and animal source
19. Classify color additives according to their approved uses. Color Additives
Approved Uses
FD & C dyes
legally used in food, drugs and cosmetics
D & C dyes
legally used in drugs and cosmetics
External D & C dyes
legally used only to color externally applied drugs and cosmetics
20. Differentiate dyes from lake pigments. Dyes are added to pharmaceutical prens in the form of diluted solutions while lakes are commonly used in the form of fine dispersions or suspension.
21. Give some factors in selecting dyes for formulations.
PHYSICAL AND CHEMICAL PROPERTIES
Solubility of the dye should be the first to be studied – in the solvent or vehicle used. Dyes may be grouped into water soluble or oil soluble.
pH Dyes can change color with a change of pH. The color must be chemically stable in the environment of the other formulative ingredients for the shelf life; dye must be photostable.
22. How is sterilization by physical methods done? It can be done thru autoclaving, the process of high-pressure sterilization by steam of media and equipment required for growing microorganisms and for cultures and waste materials prior to disposal. The recommended autoclave cycle is 20 minutes at 15 lb. pressure and 121°C, dry heat at 180°C for 1 hour. Another physical physical method method is through through bacterial bacterial filtration. filtration.
23. Name some factors in selecting preservatives. a) Prevents the growth of the type of microorganisms ( contaminants of the preparations) b) Soluble enough in water to achieve adequate concentrations in aqueous phase with two or more phase systems c) Proportion of preservative remaining undissociated at the pH of preparation (can penetrate the microorganism & destroy its integrity). d) Concentration of the preservative does not affect the safety/comfort of the patient e) With adequate stability and not reduced in in concentration by chemical decomposition/volatilization f) Compatible with all other formulative ingredients and does not interfere with them g) Does not adversely affect the preparation’s container or closure.
24. What are the mechanisms of antibacterial action? a) Modifications of cell membrane permeability and leakage of cell constituents (partial lysis); b) Lysis and cytoplasmic leakage;
c) Irreversible coagulation of cytoplasmic constituents; d) Inhibition of cellular metabolism by interfering with enzyme systems/inhibition of cell wall synthesis; e) Oxidation of cellular constituents; and f) Hydrolysis
