Advanced Pharmaceutics

• Solubility


  Depends on nature of solvent, MR, size and shape, temperature
• Noyes-Whitney equation


  Increase surface area = increase dissolution and absorption
• Excipients

  • Co-solvents
  • Microemulsions
  • Surfactants
• Co-solvents

  Toxic, e.g. polypropylene glycol, glycerine, ethanol
• Microemulsions


  Oil, water + surfactants, clear & stable, form micro-droplets, high excipient: drug ratio = low stability
• Surfactants

  • Anionic = SDS
  • Cationic = cetyl C
  • Zwitterionic = CAPB
  • Neutral = oleyl alcohol
• Surfactants in aqueous


  Spontaneous micelle aggregation
• Surfactants non-aqueous

  Reverse micelle
• High excipient: drug ratio = unstable
• Nanotechnology


  Calixarenes, cyclodextrins, liposomes
• Calixarenes


  Bucket shaped cyclic oligomers, contains hydrophobic cavity in solid and solution, low cost, less toxic
• Cyclodextrins


  Rigid conical structure, exterior = hydroxyl groups = H bonds = forms inclusion complex, good for hydrophobic drugs, not universal
• Cyclodextrins


  • Improves photostability of avobenzone (sunscreen)
• Liposomes


  Aqueous core, closed sphere, formation dependent on temperature, liquid concentration and electrostatic interactions
• Liposome classification


  • Multi-lamellar = many bilayers (1-5mcm)
  • Large uni-lamellar = single bilayer (100-250nm)
  • Small uni-lamellar = single phospholipid bilayer (20-100nm)
• Liposome shape


  Depends on amphiphile shape, expressed as critical packing parameter, truncated cone = ideal
• Liposome drug delivery


  Liposomes provide protection, not good for hydrophilic drugs, drug release controlled by bilayer modification
• Smart polymer systems

  Stimuli responsive to biological molecules, physical (light, temperature, ultrasound), chemical (pH)
• Temperature responsive polymers


  Cancerous tissue has higher temperature, polymer releases drug when exposed to higher temperature
• pH responsive polymers


  External pH of tumour cell is less than healthy cell
• Amphiphilic polymer architecture

  • Star-shaped polymers
  • Block co-polymers
  • Graft polymers
  • Dendrimers
• Star-shaped polymers


  Covalently assembled, unimolecular micelle, 3+ linear polymer chains linked to central core, e.g. paclitaxel, prednisolone
• Block co-polymers

  Self assembled, 2+ monomer types
• Graft polymers

  Self assembled (spontaneous in aqueous), hydrophilic backbone, hydrophobic stuck on, low excipient:drug = more stable
• Dendrimers


  Covalently assembled, highly branched, vector, not filtered out of circulation quickly, unable to reach renal threshold, reduce clearance, divergent (inside out), convergent (outside in), cationic (antimicrobials, cytotoxics), anionic (antivirals)
• Polymeric micelles


  Self-assembly size between 30-100nm, enter cell via endocytosis, increased efficacy, decreased toxicity
• Nanonisation


  Large insoluble drugs, drug crystals are precision milled = smaller, decrease side effects, oral delivery, pulmonary delivery
• Metallic nanoparticles

  Formed via reduction of metal salts, gold nanoparticles (chemically stable, biocompatible, absorb visible/NIR wavelengths = increases temp = cell hyperthermia), iron oxide nanoparticles (magnetic, easily aggregate in solution, overcome by adding silica and polymer, incorporated into liposomes, drug release caused by change in pH/hyperthermia, superparamagnetic iron oxide nanoparticles), gold-iron oxide hybrid nanoparticles (magnetic iron oxide core surrounded by gold, surface rich in electrons = overall negative charge, type 1 = heater, type 2 = thermosensitive linkers, type 3 = incorporated into liposomes)
• Quantum dots


  1. 10nm, use - sensors, optical, electrical devices, biomedical - fluorescent tags, sensitive to local microenvironment
• Bisnaphthalmides


  Incorporated into polymeric nanoparticles = tumour retardation, PK3
• Microneedle types

  • Solid
  • Coated
  • Dissolving
  • Hollow
  • Hydrogel forming
• Microbubbles

  1. 2nm, drug release triggered by sonoporation (ultrasound), amphiphile surrounding gaseous core
• Hydrogels


  Networks of cross linked polymer chains with H2O, increase in H2O = drug release
• Scaffolds


  Highly porous bio-compatible materials, act as tissue engineering templates, drugs incorporated or conjugated to scaffold/matrix, remotely triggered scaffolds (biodegradable that collapse after fixed time, addition of nanoparticles = enhance functionality)
• Inorganic nanoparticles


  Inorganic nanoparticles + drug molecule = theranostatic agents, inorganic nanoparticles in larger micromolecular systems used for imaging