QC

• drug stability testing


  to provide evidence on how the quality of a drug product changes with time under the influence of  environmental factors.
• drug environmental factors

  temperature, light, humidity
• Drug Stability


  to establish a re-test period for the drug substance or a shelf-life for the drug product and recommended storage conditions.
• frozen

  -10 and -25
• cold

  2-8
• cool

  8 and 15
• controlled room temperature

  20 - 25
• room temperature

  prevailing in the work area
• warm

  30 and 40
• excessive heat

  above 40
• The ICH guidelines divide the world into four climate zones

  I, II, III, IV
• common types of degradation

  zero-order degradation and first-order degradation
• Procaine Drug type

  Local Anaesthetic
• zero-order degradation


  independent of drug concentration
• zero-order degradation


  constant rate of degradation
• first-order degradation


  dependent on drug concentration
• first order degradation


  rate of degradation decreases over time as drug concentration decreases
• Tertiary aliphatic amine, pKa 9.0, Ester, neutral, Aromatic amine, very weak base, pKa ca 2


  procaine functional groups
• 26 days at pH 7.0, 37°C


  Half-life in water
• First-order


  degradation order of procaine
• Proxymetacaine , Benzocaine , Tetracaine , Propoxycaine , Bupivacaine , Lidocaine , Prilocaine


  procaine closely related drug molecules
• Analgesic


  Paracetamol Drug type
• Amide group, neutral

  Phenolic hydroxy group, very weak acid, pHa 9.5


  paracetamol functional groups
• 21.8 years at pH 6 and 25°C


  paracetamol Half-life in water
• bupivacaine, Procainamide , Lidocaine , Beclamide , Acebutolol 


  Paracetamol Other drugs containing an amide group
• Analgesic


  aspirin drug type
• Carboxylic acid, weak acid, pKa 3.5, Phenolic ester, particularly unstable


  aspirin functional groups
• 52 hours at pH 7.0 and 25°C; ca 40   days at pH 2.5 and 25°C


  aspirin Half-life in water
• Metipranolol, Vitamin E , Benorilate, Dipivefrin


  Aspirin Other drugs containing phenolic ester group:
• Antibiotic


  Benzylpenicillin Drug type
• Amid, neutral, relatively stable, Thioether, neutral, can be oxidized as high levels of oxygen stress, Lactam ring, neutral, particularly susceptible to hydrolysis, Carboxylic acid, weak acid pKa 2.8


  Benzylpenicillin Functional groups
• 38 days at pH 6.75 and 30°C


  benzylpenicillin Half-life in water
• 39 days at pH 6.5 and 25°C


  ampicillin half life in water
• Amoxicillin, Cloxacillin, Carbenicillin, Flucloxacillin, Phenoxymethylpenicillin, Cefalexin, Cefuroxime


  Benzylpenicillin Compounds with similar properties:
• Anticancer


  5-Fluorouracil Drug type
• Ureide nitrogen, acidic, pKa 7.0

  Ureide nitrogen, very weakly acidic, pKa 13.0


  5-Fluorouracil Functional groups
• Phenobarbital, Amobarbital, Bemegride, Uracil, Phenytoin, Theophylline, Theobromine


  5- Fluorouracil

  Compounds containing an acidic nitrogen in a heterocyclic ring
• B-adrenergic blocker


  Acebutolol Drug type
• Amide, neutral, susceptible to hydrolysis inder strongly acidic conditions, Aromatic ether group, potentially oxidizable under stress conditions, Secondary amine group, pKa 9.4


  Acebutolol Functional groups:
• Sympathomimetic


  Isoprenaline Drug type