unit 1(pdf)

• Biologic


  Medicinal products derived from blood, as well as vaccines, toxins and allergen products
• Biopharmaceutical


  Pharmaceutical product produced by biotechnological endeavor
• Biotechnology medicines/products of pharmaceutical biotechnology

  Any pharmaceutical product used for a therapeutic or in vivo diagnostic purpose, which is produced in full or in part by either traditional or modern biotechnological means
• Biotechnology


  The use of biological systems (e.g. cells or tissues) or biological molecules (e.g. enzymes or antibodies) for or in the manufacture of commercial products
• Pharmaceutics


  The discipline that deals with the process of turning a new chemical entity (NCE) or old drugs into a medication to be used safely and effectively by patients
• Branches of pharmaceutics


  • Pharmaceutical formulation
  • Pharmaceutical manufacturing
  • Pharmaceutical technology
• Pure drug substances are usually white crystalline or amorphous powders
• The clinical performance of drugs depends on their form of presentation to the patient
• Formation of pharmaceutical/chemical companies such as Bayer and Hoechst


  Late 1800s
• Scientists at Bayer succeeded in synthesizing aspirin


  1895
• Large-scale industrial production of insulin commenced

  1920s
• Pharmaceuticals of animal origin

  • Therapeutic proteins
  • Steroid (sex) hormones
  • Corticosteroids
  • Prostaglandins
• Most of these animal-derived pharmaceuticals are now prepared synthetically
• Chemical families of plant-derived medicines

  • Alkaloids
  • Flavonoids
  • Terpenes and terpenoids
  • Steroids (e.g. cardiac glycosides)
  • Coumarins
  • Quinines
  • Salicylates
  • Xanthines
• Better-known plant derived drugs


  • Listed in Table 1.16
• Antibiotics


  Pharmaceuticals of microbial origin, produced by a wide variety of secondary metabolites
• Over 10,000 antibiotic substances have been isolated and characterized
• Over half the antibiotic substances described to date are produced by the bacterial order Actinomycetales, particularly the genus Streptomyces
• Penicillins


  A family of both natural and semi-synthetic antibiotics with a 6-aminopenicillanic acid core ring structure
• Naturally produced penicillins include penicillins G and V
• Semi-synthetic penicillins can be manufactured by enzymatic removal of a natural penicillin side-chain and attachment of novel side-chains
• Some semi-synthetic penicillins are effective against bacterial pathogens resistant to natural penicillins, and others are acid stable for oral administration
• Traditional pharmaceuticals


  Low molecular weight organic chemicals, mostly manufactured by direct chemical synthesis
• Biotechnology-derived pharmaceuticals


  Hormones, blood products and other substances produced by/extracted from biological sources
• Some pharmaceuticals involve a combination of chemical synthesis and biotechnology, such as semi-synthetic antibiotics
• Early effective drugs


  • Digitalis
  • Quinine
  • Ipecacuanha
  • Mercury
• Advantages of biopharmaceuticals


  • Overcome problems of source availability
  • Overcome problems of product safety
  • Provide an alternative to direct extraction from inappropriate/dangerous source material
  • Facilitate generation of engineered therapeutic proteins with clinical advantages over native proteins
• Stages of drug development process

  • Drug Discovery
  • Initial characterization
  • Pre-clinical trials
  • Regulatory approval sought to commence trials in humans
  • Clinical trials (Phases I, II & III)
  • Submission of marketing/manufacturing authorization applications to regulatory authorities
  • Regulatory authorities review and grant (or refuse) marketing/manufacturing licenses
  • Product goes on sale
  • Post-marketing surveillance

  
• The entire drug discovery process takes an average of 12-15 years to complete
• Stages of drug development process

  • Basic Research Stage (Years 0-3)
  • Development Stage (Years 4-10)
  • Preclinical Testing (Years 4-6)
  • Clinical Testing (Years 7-10)
  • Registration of the drug with the U.S. Food and Drug Administration
  • Introduction of the drug to the public (Years 11+)
  • Product Surveillance (Years 11+)

  
• Lipinski's Rule of Five


  A set of criteria to predict drug-likeness and oral bioavailability, based on molecular properties like hydrogen bond donors/acceptors, molecular mass, partition coefficient
• Lipinski's Rule of Five criteria

  • No more than 5 hydrogen bond donors
  • No more than 10 hydrogen bond acceptors
  • Molecular mass less than 500 daltons
  • Octanol-water partition coefficient log P not greater than 5
• Lead-like compounds


  Compounds that meet a more stringent set of criteria (e.g. molecular weight 180-500, log P -0.4 to +5.6, polar surface area ≤140 Å2, ≤10 rotatable bonds) to be suitable as starting points for drug discovery
• Compounds that are orally active


  • 10 or fewer rotatable bonds
  • Polar surface area equal to or less than 140 Å2
• Lead-like


  During drug discovery, lipophilicity and molecular weight are often increased in order to improve the affinity and selectivity of the drug candidate
• Rule of three (RO3)

  Defines lead-like compounds as those that have: 1) octanol-water partition coefficient log P not greater than 3, 2) molecular mass less than 300 daltons, 3) not more than 3 hydrogen bond donors, 4) not more than 3 hydrogen bond acceptors, 5) not more than 3 rotatable bonds
• Preformulation


  The first learning phase where the fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder are determined before the development of major dosage forms like tablets and capsules
• Factors preformulation scientist must consider

  • The amount of drug available
  • The physicochemical properties of the drug already known
  • Therapeutic category and anticipated dose of compound
  • The nature of information a formulation should have or would like to have

  
• Preformulation drug characterization tests

  • UV spectroscopy
  • Solubility
  • Melting point
  • Assay development
  • Stability
  • Microscopy
  • Bulk density
  • Flow properties
  • Compression properties
  • Excipient compatibility
• UV spectroscopy


  A fairly accurate and simple method for quantitative estimation of drugs in early preformulation stages