Module 5 Summary PDF

MODULE 5 RIZZA A. CALUAG Pharmaceutical Jurisprudence IMPORTANT STATUTES SUMMARIZED (Must know) RA No. Common name Date RA 5921 Pharmacy Law June 23, 1969 RA 3720 Food, Drugs and Cosmetics Act June 22, 1963 RA 6675 Generics Act of 1988. September 13, 1988 RA 8203 RA 6425 RA 9165 RA 7...

MODULE 5 RIZZA A. CALUAG Pharmaceutical Jurisprudence IMPORTANT STATUTES SUMMARIZED (Must know) RA No. Common name Date RA 5921 Pharmacy Law June 23, 1969 RA 3720 Food, Drugs and Cosmetics Act June 22, 1963 RA 6675 Generics Act of 1988. September 13, 1988 RA 8203 RA 6425 RA 9165 RA 7432 RA 9257 Special Law on Counterfeit Drugs The Dangerous Drugs Act of 1972." Comprehensive Dangerous Drugs Act of 2002" Senior Citizen Act of 1992 Expanded Senior Citizens Act of 2003 July 22, 1996 April 4, 1972 June 7, 2002 April 23, 1992 February 26, 2004 RA 9994 RA 7394 RA 7581 RA 9502 Expanded Senior Citizens Act of 2010 Consumer Act of the Philippines Price Act Universally Accessible Cheaper and Quality Medicines Act of 2008 Food and Drug Administration (FDA) Act of 2009 "Traditional and Alternative Medicine Act (TAMA) of 1997." February 15 2010 April 13 1994 May 7, 1992 June 6, 2008 RA 9711 RA 8423 August 18, 2009 December 9, 1997 Amendments/ supplemental AOS EO 174 RA 10918 EO 175 AO 55 AO 56 AO 62 AO 63 RA 9165 None RA 9257 RA 9994 OO no. 1, s. 1988 Implementation of Executive Order No. 119, Reorganizing the Bureau of Food and Drugs January 26, 1988 AO no. 153, s. 2004 Revised Guidelines in cGMP in manufacturing, packing, repacking or holding food AO no. 43, s. 1999 Current Good Manufacturing Practice Guidelines For Drugs May 07, 2004 September 29, 1999 AO no. 90, s. 2002 Current Good Manufacturing Practice Guidelines For Cosmetic Products March 18, 2002 AO no. 42, s. 1982 Drug Registration of Herbal and/or Traditional Drugs, Both Local And Imported August 19, 1992 EO no. 302 Declaring and Adopting the Philippine Pharmacopoiea as The Official Book of Standards and Reference for Pharmaceutical Products and Crude Plant Drugs in the Philippines March 29, 2004 AO no. 55, s. 1988 AO no. 64, s. 1989 Requirements for Labelling Materials of Pharmaceutical Products Amendment of AO no. 55, s. 1988 December 07, 1988 March 13, 1989 AO no. 107, s. 1991 Guidelines on Dispensing Multiactive-Ingredient Fixed-Dose Combination of Drug Products AO no. 56, s. 1989 AO no. 67, s. 1989 Revised Regulations For The Licensing of Drug Establishment and Outlets May 16, 1991 January 03, 1989 Revised Rules and Regulations on Registration of Pharmaceutical Products March 15, 1989 Policy and Requirements for Availing of Compassionate Special Permit (CSP) for AO no. 4, s. 1992 Restricted Use of Unregistered Drug and Device Product/Preparation November 03, 1992 Rules and Regulations for Licensing Local Manufacturers of Vaccines and Biological AO no. 27, s. 2001 Products June 19, 2001 Rules and Regulations on the Registration, including Approval and Conduct of Clinical AO no. 47-A, s. 2001 Trials and Lot or Batch Release Certification of Vaccines and Biologic Products August 30, 2001 Rules and Regulations to Implement Prescribing Requirements under the Generics Act of AO no. 62, s. 1989 1988 March 15, 1989 AO no. 90, s. 1990 Amendment to AO no. 62, s.1989 April 23, 1990 Rules and Regulations to Implement Dispensing Requirements under the Generics Act of AO no. 63, s. 1989 1988 March 13, 1989 Ethical Principles Summarized Ethical Principle Definition Non-maleficence To do no harm Beneficence Duty to promote good Respect for autonomy Confidentiality Veracity Respect for the individual’s right to decide on issues that affect self right to give or refuse consent relative to release of privileged information obligation to tell the truth, or honesty Role fidelity Obligation UNLAWFUL ACTS & PENALTIES IMPRISONMENT 1P LIFE IMPRISONMENT TO DEATH 2P 12 YRS 1 DAY – 20 YRS 3P 6 MOS 1 DAY – 4 YRS MAXIMUM PENALTY FINE 500K- 10M 100K-500K 10K-50K 1P LIFE IMPRISONMENT TO DEATH 500K- 10M Importation of Dangerous Drugs Sale of Dangerous Drugs Manufacture of Dangerous Drugs Unlawful Prescription Cultivation or Culture Maintenance of Den, Dive or Resort of Dangerous Drugs Possession of Dangerous Drugs POSSESSION OF DANGEROUS DRUGS • • • • • • • 10 grams or more of opium; 10 grams or more of morphine; 10 grams or more of heroin; 10 grams or more of Marijuana Resin/Oil 10 grams or more of LSD,GHB 50 grams or more of Shabu 500 grams or more of Marijuana 2P 12 YRS 1 DAY – 20 YRS 100K-500K Importation of chemical Precursor or Essential Chemical Sale of chemical Precursor or Essential Chemical Manufacture of chemical Precursor or Essential Chemical Unnecessary Prescription Coddler/ Protector Illegal diversion of any controlled precursor and essential chemical Maintenance of Den, Dive or Resort of chemical Precursor or Essential Chemical 3P 6 MOS 1 DAY – 4 YRS 10K-50K Possession of Equipment, Instrument, Apparatus and Other Paraphernalia for Dangerous Drugs Drug User MAXIMUM PENALTY 1. Possession of Dangerous Drugs Meetings 2. Bringing any D.D, C.P., E.C through the use of DIPLOMATIC PASSPORT 3. Selling, trading, distributing illegal substance 100 meters away from school 4. Financer and Drug sellers who use Mentally deranged people and minors Drug Delivery Systems and Manufacturing Pharmacy New Chemical Entity Pre-Clinical Studies Organic Synthesis Molecular Modification Chemistry Physical Properties Biological Pre-formulation Investigational New Drug Clinical Trials Phase 1 Phase 2 Phase 3 Pre-Clinical Studies (continued) New Drug Application (NDA) Long term animal toxicity Product Formulation Manufacturing Control Package and Label design Postmarketing (Phase 4) Philippine GMP regulation -- AO43 1999 - adoption of the 1st edition of the current GMP guidelines by FDA -- AO2012-0008 - adoption and implementation of the PIC/s GMP as the standard on the manufacturer -- FDA MC 2012- Philippine FDA mandated all drug manufacturers to ensure strict and full compliance to the newly adopted PICS Container • device that holds a drug and is or may be in direct contact with the drug 1. Well-Closed Container protects against extraneous solids and liquids, loss of drug under ordinary conditions of handling, shipment, storage and distribution 2. Tight Container protects from extraneous solids, liquids or vapors, from loss of drug and from efflorescence, deliquescence or evaporation 3. Hermetic Container impervious to air or any other gases under ordinary conditions of handling, shipment, storage and distribution generally sterile 4. Light Resistant Container protects the contents from photochemical deterioration amber, opaque, blue Materials Used for Packaging: 1. GLASS Type General Description Uses Test I II HRBSG TSLG for parenteral for parenteral PG TEST WA TEST III NP SLG GPSLG for parenteral other products except parenteral PG TEST PG TEST Powdered Glass Test • • • performed on ground/powdered glass to expose internal surface tests the leaching potential of the glass alkali titrated with 0.02 N sulfuric acid Water Attack Test • exposure of the glass with sulfur dioxide at 121ºC Plastic Materials PE - cannot be autoclave - Low-density – droppers & sprays - High-density – solid oral prepns PET - For beverages - APETG (amorphous PET glycol) - PETG (PET glycol) - have transparency and luster PP PVC - Autoclavable - Rigid & good clarity - blister packaging USP STORAGE CONDITIONS Cold Place Freezer Refrigerator Cool Room Temperature *Controlled Room Temperature Warm Excessive Heat < 8 deg C -25 to -10deg C 2-8 deg C 8- 15 deg C 20-25deg c 15-30deg C 30-40 degC ABOVE 40deg C Solubility Terms of Solubility Parts of Solvent Very Soluble <1 Freely Soluble 1-10 Soluble 10-30 Sparingly Soluble 30-100 Slightly Soluble 100-1000 Very slightly Soluble 1000-10000 Insoluble >10000 1. Purified Water obtained by distillation, ion-exchange or reverse osmosis pH 5-7 used in prescription and manufactured finished products except parenteral and other sterile solutions 2. Water for Injection purified water that is FREE of pyrogens obtained by distillation or reverse osmosis used for the preparation of parenteral solutions 3. Sterile Water for Injection -WFI that is sterilized & packaged in single-dose containers < 1L 4. Bacteriostatic Water for Injection -SWI that contains 1 or more antimicrobial agents packaged in single or multiple-dose containers <30ml 5. Sterile Water for Inhalation -Water purified by distillation or reverse osmosis & rendered sterile -Not used for the preparation of parenteral solutions or other sterile dosage forms 6. Sterile Water for Irrigation WFI that is sterilized and suitably packaged Classification of powders based on particle size: USP Standards for Powders of Animal and Vegetable drugs FINENESS SIEVE SIZE All particles that pass thru SIZE UNIT % of particles passed. Very coarse #8 236mm nmt 20% thru #60 Coarse #20 850um nmt 40% thru #60 Moderately coarse #40 425um nmt 40% thru #80 Fine #60 250um nmt 40% thru #100 Very fine All passed #80 180um No limit to greater fineness USP Standards for Powders for Chemicals FINENESS Coarse Moderately coarse Fine Very fine SIEVE SIZE All particles that pass thru SIZE UNIT % of particles passed. #20 #40 850um 425um nmt 60% thru sieve#40 nmt 60% thru sieve #60 #80 #120 180um 125um no limit to fineness no limit to greater fineness 1.Hopper - LOADS THE GRANULE 2. Feed shoe- DIRECTS GRANULES FROM THE HOPPER TO THE SIDE 3. Punch- COMPRESS GRANULES INTO TAB Parts of a Tablet Press (HFPDC) 5. Cam tracks-GUIDES THE MOVEMENT OF UPPER AND LOWER PUNCHES 4. Die- CONTROL THE SIZE AND SHAPE OF THE TABLET COLORANTS: • FD&C Red No. 2 (amaranth) - causes cancer in rats, unproven safety • FD&C Red No. 4 - found in maraschino cherries and ingested drugs; only used in external drugs and cosmetics • FD&C Yellow No. 5 (tartrazine) - causes allergic type reaction in many people • D & C RED No. 22 (EOSINE) • FD and C #6 (SUNSET YELLOW) • BRILLIANT BLUE- FD AND C BLUE NO.2 • ALLURA RED- FD AND C BLUE NO.40 Steps in sugar-coating (SSSFP) 1. Sealing / waterproofing-- FOR COMPONENTS EASILY AFFECTED BY WATER 2. Subcoating-- IMPROVE BOND BETWEEN SUGAR COAT AND TABLET CORE 3. Syruping / smoothing-- COMPLETE ROUNDING OFF • • • Glossing - establishing color base Heavy syruping - build a solid color base rapidly Regular syruping - to attain appropriate color 4. Finishing – TO ATTAIN FINAL SMOOTHNESS • • DEBOSSED- imprinted with a mark BELOW the surface EMBOSED- imprinted with a mark ABOVE the surface. 5. Polishing– for sheen or gloss FILM-COATING 1. Film Former - PRODUCES SMOOTH THIN FILM Examples: Cellulose acetate phthalate, HPMC 2. Alloying Substance- PROVIDES WATER SOLUBILITY / PERMEABILITY TO THE FILM TO ENSURE PENETRATION BY BODY FLUIDS Ex. polyethylene glycol (PEG) 3. Plasticizer - PRODUCES FLEXIBILITY + ELASTICITY DURING APPLICATION Ex. Castor oil, PG, Glycerin, PEG, 4. Surfactant - ENHANCE SPREADABILITY OF THE FILM DURING APPLICATION Ex. Spans & Tweens 5. Opaquant & Colorant- TO ENHANCE AESTHETIC QUALITIES OF THE COAT ex. TiO2, FD&C 6. Sweetener, Flavor and Aroma - ENHANCE ACCEPTABILITY OF THE TABLET BY THE PX Ex. vanillin, saccharin 7. Glossant - PRODUCES LUSTER TO TABLET Ex. Beeswax 8. Volatile Solvent - ALLOWS THE SPREAD OF OTHER CMPD OVER THE TABLET WHILE ALLOWING RAPID EVAP TO PERMIT AN EFFECTIVE YET SPEEDY OPERATION Ex. alcohol-acetone mixture SPANSULE: - A capsule composed of hard gelatin shell containing hundreds of tiny coated beads/pellets of drugs for sustained release. - Ends of both bodies and cap are highly tapered/narrowed. Used by Smith Kline Beecham. PULVULES - End of the body-producing peg is tapered but the cap-making peg is rounded. Used by Eli Lilly. KAPSEAL -This is a distinctive looking capsule because of the sealing with a colored band of gelatin. This is used by Parke-Davis. Coni-Snap - The rim of the capsule body is not straight but tapered slightly. This eliminates splitting of the joined capsule. A pH-sensitive, non-digestible radiofelemettric device used as a nonradioactive means of measuring gastric pH, gastric residence time and gastric emptying time of solid dosage forms is called HEIDELBERG CAPSULE. • Lontabs is an example of specially coated beads • Endurates is an embedded drug in a slowly eroding matrix • Durabond forms slowly dissolving complexes that is insoluble in body fluids • Gradumet is an example of drug in an inert plastic matrix. HLB Value Range 0-3 Surfactant Application 4-6 W/O emulsifying agents 7-9 Wetting agents 8-18 O/W emulsifying agents 13-15 Detergents 10-18 Solubilizing agents Antifoaming agents Transdermal administration Electroporation is a TDDS enhanced by the application of short, high-voltage electric pulses to create aqueous pores in the lipid bilayer of skin and thereby facilitate drug diffusion. Iontophoresis is a TDDS enhanced by the use of applied electric current to facilitate drug diffusion through the skin. Phonophoresis is a TDDS enhanced by the application of lowfrequency ultrasound to facilitate drug diffusion through the skin. High velocity powder particles A transdermal drug delivery system using supersonic shock waves of helium gas to enhance drug diffusion through the skin Suppository Bases: 1. Fatty / Oleaginous Bases 2. Water-Soluble and Water-Miscible Bases 3. Miscellaneous Bases • Fattibase, Wecobee bases, Witepsol base, Cocoa butter • Cocoa butter • good base for rectal suppository • melting just below body temperature and yet maintaining its solidity at usual room temperatures • glycerinated gelatin, PEG • are mixtures of oleaginous and watersoluble or water-miscible materials Ointment Bases 1. OLEAGINOUS - hydrocarbon bases - not water-washable, incorporation of water with some degree of difficulty PETROLATUM WHITE PETROLATUM YELLOW OINTMENT WHITE OINTMENT (USP) MINERAL OIL Ointment Bases 2. ABSORPTION are not easily removed from the skin A. Anhydrous type those that permit the incorporation of aqueous solutions resulting in the formation of w/o emulsions HYDROPHILIC PETROLATUM USP ANHYDROUS LANOLIN AQUAPHOR AQUABASE POLYSORB B. Hydrous type those that are w/o emulsions that permit the incorporation of additional quantities of aqueous solutions COLD CREAM HYDROCREAM LANOLIN EUCERIN NIVEA CREAM Ointment Bases 3. WATER-REMOVABLE BASES - are o/w emulsions resembling creams - easily washed from the skin, hence called “water-washable” DERMOVAN HYDROPHILIC OINTMENT USP, UNIBASE VANISHING CREAM Ointment Bases 4. WATER-SOLUBLE BASES - do not contain oleaginous components - are completely water-washable, hence called “greaseless” PEG OINTMENT POLYBASE PG PEG Actuator – provides a rapid and convenient means for releasing the contents from a pressurized container; button that activates the system Valve – expels the contents from the container; regulate the flow of product from container Stem – Part of the usual aerosol valve assembly that supports the actuator and delivers the formulation in the proper form Dip tube – the tube that delivers the content Gasket – Placed snugly with the stem, prevents leakage of the formulation when the valve is closed. Mounting cup – Part of the usual aerosol valve assembly that is attached to the aerosol can or container and hold the valve in place. Spring – Holds the gasket in place and is the mechanism by which the actuator retracts when pressure is released, returning the valve to the closed position 1. The most commonly used class of aerosol propellant which is composed of butane, iso-butane and propane gasses. It has excellent solvent powers; A.Hydrocarbon propellants C. Hydrofluroalkanes B. Chlorofluorocarbons D. Compressed Gas propellants 2. A class of aerosol propellants, which require the use of a non-volatile co solvent. It produces only coarse droplets and is applicable only to surface and topical sprays; A. Hydrofluroalkanes C. Hydrocarbon propellants B. Compressed Gas propellants D. Chlorofluorocarbons 3. It is a Zwitterionic type of an aerosol propellants; A. Oleic acid C. Cetyl pyridinium chloride B. Phosphatidylcholine D. Sorbitan trioleate 4. An aerosol container material, which is lightweight and seamless. And is mostly used for inhalation and topical aerosols; A. Three-piece tin plate C. Plastic coated glass B. Plastic D. Plastic 5. An aerosol container material, which can be pressurized from the base with compressd gasses. Visible seams make this container visually less appealing; A. Aluminium glass C. Plastic coated glass B. Three-piece tin plate D. Plastic Manufacture of sterile product Should be carried out in clean areas, entry to which should be through airlocks for personnel and/or for equipment and materials Clean areas An area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce the introduction ,generation, and retention of contaminants within the area Airlock An enclosed space with two or more doors, which is interposed between two or more rooms Grade A -- Local zone for high risk operations -- EX: Filling zone, stopper bowls, open ampoules and vials, , aseptic connections -- provided by a laminar air flow work station with a HEPA Grade B -- For aseptic prepn and filling Grade c and d -- clean areas for Carrying out less critical stages of the manufacture of sterile Grade C -- Hair and where relevant beard should be covered -- A single or two piece suit gathered at the wrist and with high neck and appropriate shoes or overshoes should be worn should shed virtually no fibers or particulate matter Grade D -- Hair and where relevant beard should be covered -- General protective suit and appropriate shoes and overshoes should be worn -- Appropriate measures should be taken to avoid any contamination coming from outside and clean areas Production facilities- 5 sections a. Materials support area -- surfaces should be continuous class 10,000 environment ( nmt 10,000 particles or 0.5 um or larger are present in per cubic ft.) b. Compounding area -- most stringent control stainless steel cabinets and counters -- continuous surfaces -- class 100 environment c. Aseptic filling area -- “heart” of production area laminar air flow (LAF) with HEPA filter (High Efficiency Particulate Air) -- 99.95% efficiency -- Used to test efficiency of hepa filter: DOP TEST d. Quarantine area storage while waiting for QC results e. Finishing area STERILIZATION METHODS Type 1. Moist heat/ steam sterilization Principle Protein denaturation Applications Equipment Notes Solutions in sealed Autoclave containers and ampules (121ºc, 15-30 mins, 15psi) 2. Dry heat sterilization Oxidation Oils and dry powders Hot air oven (160-170ºc, 2-4 hrs) 180 oC for 4 hrs 250 oC for 45 mn 650 oC for 1 min 3. Radiation/ cold sterilization Mutation Glasswares and equipment UV light (240-280 nm) 4. Gas sterilization Protein denaturation Gas chamber with ethylene oxide Thermolabile substances 5. Filtration Physical removal Membrane filters Thermolabile substances Bubble testused to measure the efficiency of membrane filter Sterilization Biological Indicators 1. Steam: B. stearothermophilus 2. Dry Heat: B. subtilis 3. Ionizing Radiation UV: B. pumilus 4. Ethylene Oxide: B. subtilis SOME STUFFS FOUND IN PACOP HOMOGENIZER An equipment used to produce fine emulsion droplets, by first compressing the liquid with a high pressure and then allowing the liquid to escape radically past a flat disc, held by strong spring mechanism; CHILSONATOR A method of preparing tablet granulations, wherein the powders are de-aerated and passes between two rollers, forming a thin cake, which is screened to form granules; TWIN OR V SHELL BLENDER An equipment, which alternately combine and draw apart the tablet material, as this equipment revolves. Ideal for precise blending of dry-to-dry or dry-to-liquid materials, with short processing times; GRANULATOR/FLUID BED DRYER An equipment, which delivers a reliable and uniformly mixed dried product, without the necessity for pre-mixing. It produces a dry granulation from a wet powder mix; Vibratory Cutting mill Paar Calorimeter The most efficient type of motion in sieving Type of mill used for tough, fibrous materials Determination of moisture for effervescent tablets is conducted through: Rotor stator Type of mill used for the reduction of solid particle size and for dispersion of suspensions containing poorly wetted solids Hammer mill Ball mill/pot mill/jar mill Striking effect Produces pulverization with minimal lost of drugs Terpineol clarifying agent in the formulation of shampoos Behemic acid Opacifying agent Ceresin and ozokerite Stiffens the cream Nitrogen Anti-oxidant in parenterals Sorbitol in Al OH gel Viscosity builder Cetyl Alcohol Minimize the foam Ethocel Ethyl cellulose- binder TEA Emulsifying agent carbomer Cost effective thickener nitrocellulose Primary film former Butane, Isobutane, Propane HC bases: Excellent solvent power Polyurethane/cheesecloth Used in pan polishing Polyethylene Used for ophthalmic solution Manihot esculenta Tapioca starch Tragacanth Forms a heavy mucilage in water Physical Pharmacy FORCES OF ATTRACTION A. Intramolecular forces 1. Ionic Bond - Transfer of electron 2. Covalent Bond - Sharing of electron B. Intermolecular forces 1. Van der waals - Keesom, Debye, London KODD, DIDID, LDIDID 2. Ion Dipole - polar molecules are attracted to either positive/negative charges 3. Ion-Induced dipole - the force of attraction induced by a close proximity of a charged ion into a non-polar molecule 4. Hydrogen Bonds - attraction of H for a strongly electronegative ion 1. BOYLE’S LAW P1V1=P2V2 2. CHARLES’ LAW T1/V1 = T2/V2 3. GAY LUSSAC’S P1/T1 = P2/T2 4. COMBINED GAS LAW Ideal Gas Law PV = nRT STP- Standard Temperature Pressure 5. REAL GAS EQUATION Van der Waals eq. for real gases (P +an2/v2) (V-nb) =Nrt 6. HENRY’S LAW OF GAS SOLUBILITY states that the amount of gas dissolved in a solution is proportional to the partial pressure of the gas in equilibrium with the solution -- increased pressure, increased gas solubility 7. DALTON’S LAW OF PARTIAL PRESSURE -- states that the total pressure in a mixture of gases is equal to the sum of the partial pressure of each gas -- the partial pressure is the pressure a gas would exert if it alone occupied the whole volume of the mixture 8. GRAHAM’S LAW --speed of diffusion of gas is inversely proportional to the density METHODS OF ADJUSTING ISOTONICITY CLASS 1 - Addition of a tonicity adjusting agent CLASS 2 - Addition of water and dilution with buffered isotonic solution Cryoscopic Method Sprowl’s Method E Value Method White Vincent Method E value - gram of NaCl equivalent to 1 gram of substance Isotonic NaCl Concentration - 0.9% (w/v) NaCl Cryoscopic Method Based on the adjustment of freezing point of a solution to -0.52degC NaCl Equivalent method Based on the adjustment of freezing pt of a solution to 0.9% NaCl Sprowl’s Method Based on the method of calculating values when the weight of the drug is 0.3g V=0.3g X E X 111.1 White Vincent Merhod Method of adjustment of tonicity where in a stock solution which is isotonic is added to bring solution into its volume V= W x E X111.1 USP METHOD Step 1: Calculate the amount of NaCl represented by the ingredients in the prescription. E-Value Method Step 2: Calculate the amount of NaCl that would make the volume of solution specified in the prescription isotonic. Step 3: Subtract the amount of NaCl represented by the ingredients in the prescription (Step 1) from the amount of NaCl that would make the specific volume in the prescription isotonic (Step 2). Step 4: If an agent other than NaCl, is to be used to make a solution isotonic, divide the amount of NaCl (obtained in Step 3) by the sodium chloride equivalent (E value) of the other substance. How many grams of NaCl should be used in compounding the following prescription? Rx Pilocarpine nitrate (E=0.23) 0.3 g NaCl qs Purified water qs 30.0 mL Make isotonic solution Sig. for the eye Step 1. 0.23 x 0.3 g = 0.069 g of sodium chloride represented by the pilocarpine nitrate Step 2. 30 x 0.009 = 0.270 g of sodium chloride in 30 mL of an isotonic sodium chloride solution Step 3. 0.270 g (from Step 2) - 0.069 g (from Step 1) = 0.201 g of sodium chloride to be used, answer. How many grams of boric acid should be used in compounding the prescription? Rx Phenacaine HCl (E=0.17) 0.6 g Chlorobutanol (E= 0.18) 0.3 g Boric acid (E=0.52) qs Purified water qs 60.0 mL Make isotonic solution. Sig. One drop in each eye. Step 1. 0.20 x 0.6 g = 0.120 g of sodium chloride represented by phenacaine hydrochloride 0.24 x 0.3 g = 0.072 g of sodium chloride represented by chlorobutanol Total: 0.192 g of sodium chloride represented by both ingredients Step 2. 60 x 0.009 = 0.540 g of sodium chloride in 60 mL of an isotonic sodium chloride solution Step 3. 0.540 g (from Step 2) - 0.192 g (from Step 1) = 0.348 g of sodium chloride required to make the solution isotonic. But because the prescription calls for boric acid: Step 4. 0.348 g ÷ 0.52 (sodium chloride equivalent of boric acid) = 0.669 g of boric acid to be used, answer How many grams of KNO3 (E=0.58) could be used to make the following prescription isotonic? Rx 0.2% Silver nitrate solution (E=0.34) 60 mL Make isotonic solution. Sig. For eye use Step 1. 0.33 x 0.12 g = 0.04 g of sodium chloride represented by silver nitrate Step 2. 60 x 0.009 = 0.54 g of sodium chloride in 60 mL of an isotonic sodium chloride solution Step 3. 0.54 g (from step 2) - 0.04 g (from step 1) 0.50 g of sodium chloride required to make solution isotonic Because, in this solution, sodium chloride is incompatible with silver nitrate, the tonic agent of choice is potassium nitrate. Therefore, Step 4. 0.50 g ÷ 0.58 (sodium chloride equivalent of potassium nitrate) = 0.86 g of potassium nitrate to be used, answer. Using the USP method for adjusting isotonicity, compute for the required volume to make 0.5g of Atropine Sulfate (E=0.13) V= W x E X111.1 Approximate Liso Values Compound Type by Valence Liso Values Non electrolyte Weak electrolyte Di-divalent electrolyte (divalent cation and divalent anion) 1.86 2.0 Uni-univalent electrolyte (single charge on each) Uni-divalent electrolyte Di-univalent electolyte 3.4 2.0 4.3 4.8 Liso of drugs- the molar concentration that will attain isotonicity based on freezing point depression of -0.52degC Liso = E (MW) / 17 E = (Liso x 17) / MW E = (1.8 x 17) / 61.8 = 0.5 pH Logarithm of H ion conc Sorensen pH scale pH >7, pH =7, pH <7 Ionization Complete separation of ions in a crystals lattice when salt is dissolve Dissociation Separation of ions in solution when the ions are associated by interionic interaction Strong Acids pH = -log (H+) Strong Bases pOH = -log[OH] pH = pKw -pOH Weak Acids pH = - log √CAKa Weak Bases pOH = - log √ CBkb Sorensen’s buffer Basic solution of dibasic Sodium Phosphate - Used by Timolol eyedrops to obtain a pH of 6.5 BORATE BUFFER SYSTEM Feldman’s Buffer BORIC ACID, NaCl, ALKALINE SOLN CONTAINING SODIUM BORATE Atkins and Pantin Buffer BORIC ACID AND NaCl AND ALKALINE SOLN OF SODIUM CARBONATE Gifford Buffer BORIC ACID AND KCl AND ALKALINE SOLN OF SODIUM CARBONATE Acetate- most Biological Buffer System: important buffer Phosphate, Oxyhemoglobin and of blood. Carbonates Surface Tension Measurement Du Nouy measures the maximum pull on the ring by the surface Wilhelmy plate measures equilibrium surface or interfacial tension Pendant Drop based on the shape of the drop. Bubble Pressure based on the pressure Volumetric Tensiometers based on the size of the drops Measuring Surface Area Method 1: Adsorption Method Method 2: Air-permeability method Quantasorb- This instrument is generally used for surface area determination by gas adsorption and air permeability method. Optical Kinetic Electric Properties of Colloids Faraday Tyndall effect- Ability to scatter or to dispersed light. Brownian Motion – random collisions of particles resulting to irregular zigzag path Diffusion – spontaneous movement of the particles from a region of higher concentration to one lower concentration until the concentration of the system is uniform throughout. 1. Nernst Potential -- Difference between the potential of the actual surface and the electroneutral region of the surface. 2. Zeta Potential -- Difference between the potential of the surface of the tightly bound layer and the electroneutral region of the surface. Newtonian Unit for viscosity: Poise Cgs unit for poise: dyne-sec/cm2 Stress versus strain rate curve is linear. • F is directly proportional to G • Constant Viscosity with increasing rate of shear • Dependent only on temperature EX: water, air, gasoline, honey, glycerin, milk, oil in salad dressing, benzene Non-Newtonian • Substances that fail to follow Newton’s equation to flow • Exhibit VISCOELASTICITY 1. Plastic (Bingham body) - Substances that exhibit yield value - the yield value must overcome in order for the system to flow Ex: flocculated particles in suspension drilling mud, slurries, toothpaste, blood, butter, maragarine 2. Pseudoplastic (Shear thinning system) - Decrease viscosity, Increase rate of shear Ex: natural and synthetic gums, liquid dispersion of tragacanth, Na alginate, methylcellulose and Na CMC 3. Dilatant (Shear thickening system) - Increase Viscosity with Increasing Rate of shear - exhibited by suspension with high percentage of dispersed solids (>50% of the particle ) Ex: paint, whipped cream, corn starch, clay slurries Henderson Hasselbach Eq Buffer Van Slyke Eq. Buffer Capacity Fick’s Law Rate of Diffusion(Passive) Stoke’s Law Sedimentation Rate Michaelis Menten Kinetics Active Diffusion Noyes Whitney Dissolution Hess Law Proposed Heat of Summation Poiseuille Eq. “Radius of the tube- has the greatest influence on the rate of flow of liquid though a capillary tube” Amagat’s Law Gives direct opportunity between shear stress *states that the extensive volume of a gas mixture is equal to the sum of volumes of the K component gases, if the temperature T and the pressure p remain the same FARADAY’S LAW The passage of 96,500 coulombs of electricity through a conductivity cell produces a chemical change of 1 gram equivalent weight of any substance. Langmuir Proposed the monolayer theory of gas adsorption on solid surface Arrhenius equation An equation used to determine the contact angle Schulz-Hardy rule According to this rule “the higher the velocity of the ion, the greater is the precipitating power”. Regnault and Meyer Used to determine the MW of easily vaporized liquid Young’s equation Equation used to determine the contact angle BIOPHARMACEUTICS CLASSIFICATION OF DRUGS CLASS 1 INCREASE SOLUBILITY, INCREASE PERMEABILITY DILTIAZEM, PROPRANOLOL, ACETAMINOPHEN GLIPIZIDE, NIFEDIPINE CLASS 2 DECREASE SOLUBILITY, INCREASE PERMEABILITY CLASS 3 INCREASE SOLUBILITY, DECREASE PERMEABILITY INSULIN, ACYCLOVIR CLASS 4 DECREASE SOLUBILITY, DECREASE PERMEABILITY TAXOL, HCTZ PRACTICE QUESTIONS • 1. Cold Cream, USP is also known as: A. Petrolatum Rose Water Ointment B. Vanishing Cream C. Wool fat Ointment D. Rose Water Ointment 2. These type of preparation are small, cylindrical in shape administered by implantation and are prepared by implantation A. Lozenges B. Pellets C. Chewable tablets D. NOTA 3. This type of containers is impervious to air or any other gas A. Light resistant containers B. Hermetic containers C. Tight containers D. Single dose containers E. AOTA 4. This is added to Collodions to make them flexible: A. Olive oil B. Gelatin C. Castor oil D. Camphor 5. Concentration of “Diluted Alcohol” by volume is: A. 10% B. 50% C. 70% D. 20% 6. Clear, colorless, odourless, liquid, sterilized and suitably packaged and contains no bacteriostatic agent A. Sterile Water for Injection B. Bacteriostatic Water for Injection C. Water for Injection D. Distilled Water 7. This type of extract is suitable for use in ointments and pastes: A. Semiliquid B. Pilular C. Powdered D. Any 8. Mineral Oil is also known as: A. Liquid Paraffin B. Paraffin C. Petroleum Jelly D. White Ointment 9. In percolation, “to percolate slowly” means the rate of flow is: A. 1 to 3 mL/minute B. Not exceeding 1 mL/minute C. 3 to 5 mL/minute D. 5 to 10 mL/minute 10. USP defines Type I glass as 1. Treated soda lime glass 2. Intended for parenteral products 3. Resistant to leaching alkali A. 1 and 2 B. 2 and 3 C. 2 only D. 1, 2 and 3 11. The pressure required to push the air through a liquid saturated filter A. Bubble point B. Flash point C. Saturation point D. AOTA • 12. The containers used to package drugs may consist of several components. This term best describes the release of an ingredient from packaging components into the actual product • A. Sorption • B. Leaching • C. Permeation • D. Porosity • 13. The USP medicine dropper when held vertically delivers how many drops of water? • A. 15 drops of water • B. 18 drops of water • C. 25 drops of water • D. 20 drops of water 14. Compute for the E value of Papaverine sulfate HCl (MW 376) which is a 2 ion electrolyte dissociating 80% in a given concentration. A) 0.1554 B) 0.1555 58.5 1. 8 C) 0.1556 E = ------------- x --------------- = 1.8 376 D) 0.1557 15. Prohibited drugs, EXCEPT A. Morphine B. Phenobarbital C. Meperidine D. Codeine 16. The following conditions ay be used to destroy pyrogens, EXCEPT: A. 121 oC for 15 mins B. 180oC for 4 hours C. 250 oC for 45 mins D. 650 oC for 1 min 17. Kristine Kate, a 2-year old child is suffering from fever and vomiting. As pharmacist, what would you recommend to the doctor to be the most appropriate dosage form to treat fever in this case? A. Suspension B. Suppository C. Syrup D. Injection 18. Which technique is typically used to mill camphor? A) trituration B) levigation C) pulverization by intervention D) geometric dilution A.SMECTIC – SOAP LIKE/ GREASE LIKE/ ROTATES IN ONE AXIS/ MOBILE IN 2 DIRECTIONS/ MOST PHARM.IMPT B. NEMATIC– THREAD LIKE/ ROTATES IN ONE AXIS/ MOBILE IN THREE DIRECTION 19. Type of liquid crystal in which the molecules are mobile in 2 directions and can rotate about 1 axis A. Nematic B. Cholesteric C. Smectic D. Both B and C 20. Type of liquid crystal in which the molecules are mobile in 3 directions and can rotate about 1 axis A. Nematic B. Cholesteric C. Smectic D. Both B and C 21. HLB value of o/w emulsifier A. 3-6 B. 8-18 C. 15-20 D. 7-9 Comminution Particle size reduction Principal Means of Milling 1. Cutting / shearing mill (CUTTIING) 2. End runner mill- (Compression) 3. Hammer mill, vibration mill(Impact) 4. Ball mill, pin mill, Fluid energy mill (Impact and attrition) 5. Roller mill- (attrition & compression) 22. One of the basic actions involved in comminution which involves the operation of hammers or bars at high speeds A. Attrition B. Rolling C. Impact D. Mixing 23. Amount of morphine subject to life imprisonment to death penalty and a fine of 500,000 pesos to 10M pesos: A. 500g B. 50g C. 10g D. 1g 24. Compute for the specific gravity of potassium dichromate (K2Cr2O7) if its weight t in air =5.76g and its weight in oil 3.08g. The sp.gr of the oil is 0.86. A. 1.86 B. 1.85 C. 1.87 D. 1.88 Sp. Gr = [ wt. in air/ (wt. in air – wt. in oil)] x sp. Gr of oil 25. An ordinary prescription shall be preserved for a period of_______. A. 5 years B. 1 year C. 3 years D. 2 years 26. Soda lime glass: ______ A. Type I glass B. Type II glass C. Type III glass D. General purpose soda-lime glass 27. Water attack test is intended for: A. Highly resistant borosilicate glass B. Treated soda-lime glass C. Soda-lime glass D. General purpose soda-lime glass 28. The general behavior of gasses with variations of pressure, volume and temperature can be given by the _____ A. Boyle’s law equation B. Charle’s law equation C. Gay-lussac law equation D. Ideal gas law 29. Alcohol content of elixirs: A) 15-18% B) 10-40% C) >60% D) no alcohol content 30. Type of gelatin prepared from acid hydrolysis A) Type A B) Type B C) Type C D) Type D 31. BCS Classification with high permeability and low solubilty? A) Class I B) Class II C) Class III D) Class IV BIOPHARMACEUTICS CLASSIFICATION OF DRUGS CLASS 1 INCREASE SOLUBILITY, INCREASE PERMEABILITY DILTIAZEM CLASS 2 DECREASE SOLUBILITY, INCREASE PERMEABILITY NIFEDIPINE CLASS 3 INCREASE SOLUBILITY, DECREASE PERMEABILITY INSULIN CLASS 4 DECREASE SOLUBILITY, DECREASE PERMEABILITY TAXOL 32. Most preferred container for aerosols A) Tin plated B) Aluminum C) Glass D) Stainless stell 33. Government agency who issued national identification card and purchase slip booklet to senior citizen a. BFAD c. OSCA b. DILG d. DOLE 34. __________ is a list of drug which cure the vast majority of illness, affordable and available to all persons a. EDL c. USP/NF b. NDF d. None 35. Which of the ff. systems is referred to as “shear thickening”? a. Plastic c. Newtonian b. Pseudoplastic d. Dilatant