M-BIOPHAR

• Disintegration


  Physical break-up of an intact dosage form to its component aggregates
• Disintegration of dosage forms

  • Orally dispersible tablet
  • Film coated tablet
• Orally dispersible tablet


  Disintegrates faster than film coated tablet
• Disintegrants


  Substances that facilitate the disintegration of a dosage form
• High amount of disintegrating agent in formulation


  Dosage form is easily dispersed
• High amount of disintegrating agent in formulation (for acid labile drug)

  Drug is prematurely degraded, leading to subtherapeutic or no response
• Complete disintegration (USP definition)


  Residue is a soft mass with no palpably firm core
• Disintegration test


  1. Place dosage form in vessel with medium at 37°C

  2. Observe disintegration
• Dissolution


  Process where a solid drug particle is formulated into a solution
• Syrup and suspension undergo dissolution
• Dissolution process


  1. Disintegration

  2. Passive diffusion

  3. Absorption
• Solid drug particles cannot diffuse or traverse cell membranes
• Drug in solution needs to dissolve before entering the body</b>
• Dissolution tests are used to predict bioavailability
• Capsule


  Dissolves faster than tablet
• Manufacturers may modify salt forms to improve solubility
• Noyes-Whitney equation


  Describes dissolution rate
• Losartan alone is less soluble, so manufacturers add potassium salt to improve solubility
• Absorption


  Process where drug enters systemic circulation and bloodstream
• IV drugs do not undergo absorption
• Not all parenteral drugs undergo absorption (e.g. IM, SC)
• Absorption


  Rate and extent of drug entry into systemic circulation
• Some ointments are absorbed and diffused into systemic circulation (e.g. nitroglycerin ointment)
• Passive diffusion factors


  • Membrane concentration difference
  • Particle size
  • Partition coefficient
  • Degree of ionization

  
• Fick's law of diffusion

  Flux is proportional to concentration gradient, area, and permeability, and inversely proportional to membrane thickness

  
• Particle size


  Inversely related to rate of absorption
• Partition coefficient


  Directly related to lipophilicity and absorption
• Degree of ionization


  Unionized drugs are better absorbed
• Physiological factors affecting absorption

  • Degree of perfusion
  • Gastric emptying time
  • Gastrointestinal motility
  • Surface area of absorbing environment
  • Effects of disease states
• Gastric emptying time


  Inversely related to absorption rate
• Factors increasing gastric emptying time: stress, heavy exercise, gastric ulcer, heavy meal, lying on left side
• Factors decreasing gastric emptying time: extremes of food temperature, mild exercise, lying on right side
• Gastrointestinal motility


  Promotility drugs speed up absorption, antimotility drugs slow down absorption
• Main absorption site is small intestine (jejunum and ileum)
• Increased surface area (villi and microvilli) facilitates faster and greater absorption
• Disease states like IBS and vitamin B12 deficiency can affect absorption
• Calamine


  Pink, odorless, & almost tasteless powder
• The image is already formulated into solution (lotion)
• Calamine passes through 100 mesh (number of linear per inch) sieve
• Solubility of Calamine


  • Insoluble in water
  • Completely soluble in mineral acids