Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
33 Cards in this Set
- Front
- Back
|
Excipients and Definitions
|
-Excipient is an inactive ingredient of a dosage form
-Pharmaceutical ingredient = pharmaceutical excipient -Pharmaceutical active ingredient (API) = drug substance (DS) -excipient may provide stabilization |
|
|
Why Study Excipients?
|
-A final dosage form requires both API and excipients
-The properties of the final dosage form (e.g. stability, bioavailability) are highly dependent on excipients -It could be an invention in excipients chosen, their concentration, their interaction with API or among themselves |
|
|
Knowledge about Excipients
|
It critical to know excipients & their:
-Physical properties -Chemical properties -Safety -Handling -Regulatory status -Novel excipient mixtures -New excipients -food ingredients cannot be pharmaceutical ingredients -food - requirements are less strict than pharmaceutical ingredients |
|
|
Roles of Excipients in Dosage Forms
|
-Excipients establish the primary feature of the product
-Physical form -Stability -Drug release -Texture -Taste -Appearance |
|
|
Excipients in Solution Dosage Forms
|
-Solvent: to dissolve DS (drug substance)
-Flavors: palatable -Sweeteners: palatable -Colorant: appeal -Presevatives: prevent microbial growth -pH agents: to stabilize, or to dissolve DS -Antioxidant or chelating agents: to stabilize |
|
|
Examples of Excipient in Solutions
|
Solvents:
-Water: purified water or water for injection -Alcohol -Corn or soybean oil -Mineral oil Sweetening agent: to impart sweetness -Sucrose -Aspartame -Mannitol |
|
|
Selection of Excipient-Taste Masking
|
-Cocoa-flavored vehicles are effective in masking bitter taste
-Fruit or citrus flavors mask sour or acidic taste -Cinnamon, raspberry, or orange: mask salty drugs -Children like sweet and fruit flavors -Adult prefer less sweet with a tart flavor |
|
|
Excipients in Parenteral Dosage Forms
|
-Parenteral products: injectable products
-pH adjusting agents: saftey, solubility or stability --> pH can cause diff. physiology -Solvents, co-solvents: solubility -Surfactants: solubility -Antioxidants or chelating agent: stability -Preservatives: inhibit microbial growth -Isotonic agent: same osmotic pressure as blood, safety -IV solns. have to be compatible w/ blood osmotic pressure --> adjust ionic strength |
|
|
Examples of Excipients in Parenterals
|
-pH adjustment: phosphate buffer systems
-Co-solvents: Propylene Glycol, alcohol, PEG 300 --> MW- higher MW = longer polymer = more solid -Surfactants: Tween 80, Cremphor -->weakness = strong immune rxns --> used for taxol -Antioxidants: sodium metabisulfite -Chelating agent: EDTA -Preservatives: benzyl alcohol, propyl parabens -Isotonic agent: sodium chloride |
|
|
Excipients in Semi Solid Dosage Forms
|
-Semi Solid Dosage Forms are creams, ointment, suppositories
-Oil phase -Aqueous phase (can't mix with oil phase) -Emulsifying agent and surfactant --> not stable b/c particles are small and form glomerates to reduce surface area -Viscosity - increasing agent --> to make mobility smaller so particles won't collide -Stability |
|
|
Examples of Excipients in Creams
|
-Emulsifying agent, surfactant: to disperse fine droplets, reduce surface tension
*Polysorbate 80 (or Tween 80) *Sorbitan monooleate (or Span 80) -Glyceryl monostearate -Viscosity-increasing agent: to thicken *Alginic acid *Caromer *Carboxymethylcellulose sodium (CMC sodium) *Povidone --> not natural *Sodium alginate --> tested in humans during WWII --> used to increase volume of blood. Pharmacy is conservative - even though we have knowledge, can't afford to do toxicity studies. -Most are natural polymers |
|
|
Excipients in Solid Dosage Forms - Tablets
|
-Diluents or fillers: increase the bulk of tablets
-Binders: to cause adhesion in granulation -Lubricant (antiadherent): to assist tablet ejection in production -Disintegrating agents: to promote tablet break up after administration -Coating: to improve stability, to control drug release, to enhance appearance |
|
|
Examples of Excipients in Tablets
|
-Diluent (tablet): create bulk, compression, and flow
*Microcrystalline Cellulose *Lactose *Maltodextrine *Mannitol *Pregelatinized starch (Starch 1500) -Lubricant (antiadherent): to assist tablet ejection in production *Magnesium stearate --> from a mineral *Talc |
|
|
BSE or TSE Concern with Excipients
|
-Mad Cow disease
-Bovine Spongiform Encephalopathy (BSE) -BSE is a part of TSE disease (Transmissible Spongiform Encephalopathies) -Do not use excipients from any BSE or TSE contaminant area -Excipients should be free from any BSE or TSE contaminant -Certify the excipients are not from any BSE or TSE incident area -Do not use animal derived excipients, e.g. lactose |
|
|
Replacing Lactose
|
Lactose is an animal derived product
-Lactose is an excipient widely used in tablets or capsules -Low cose and function as dilent, hard to replace -Replacing lactose in formulations: *Microcrystallin Cellulose *Maltodextrine *Mannitol *Pregelatinized starch (Starch 1500) |
|
|
Coating of Pharmaceutical Dosage Forms
(Title) |
Title
|
|
|
Why Coating
|
Stability: protecting from moisture, air, light
-Modify drug release: enteric coating, sustained or controlled release -Masking: tase of odor e.g. primerate (natural) --> for hotflashes. Derived from horse. Odor is not pleasant--> therefore sugar coated. Sugar = thick barrier. Film = Thin barrier -Ease of swallow -Product Identity --> prevent mixing up -Facilitate processing: packaging, counting, eliminate dust -Appearance: esp. spotty tablets -Reducing interaction of incompatible components -Mechanical strength: protecting from abrasion or attrition -Barrier - stop anything from permeating -drug won't be dissolved at low pH in stomach |
|
|
Coating Processes
|
-Sugar coating
-Microencapsulation -Compression coating -Film coating |
|
|
Sugar Coating
|
-Main coating material: sucrose
-Substrate: tablet core (only) -Most elegant coating -Need skills -become less popular due to complicated process |
|
|
Sugar Coating Processes
|
-Sealing
-Subcoating -Smoothing -Color coating -Polishing -Printing |
|
|
Film Coated Dosage Forms
|
-Deposition of a thin polymeric film onto the dosage form from solutions.
-Manufacturing process *Spray coating solution to substrate on a moving bed -Coating Substrates: *Tablets *Capsules *Multi-particulates *Granules *Powder *Nonpareils --> sugar core; many particles of sugar coated by drug |
|
|
Film Coated Dosage Forms Advantages
|
-Low weight gain (2-3%) --> sugar coating --> as much as 30% weight gain
-Short process times --? sugar coating --> 30 hrs. -High efficiency and output -Flexibility in formulations -Less chipping of the coating |
|
|
Coated Multi-Particulates
|
Formulation approahces for cores
-Drug-loaded non-pareils --> drug continues to coat layers 0Spheronized or irregularly shaped granules -Drug crystals -Drug/ion-exchange resin complexes -Mini-tablets --> pharm. tech. term. Small beads --> 4-5 caps inside --> get 4-5 mini-release |
|
|
Coating Tablets
|
Coating tablets for function, appearance, or packaging
|
|
|
Film Coated Dosage Forms - Controlled Drug Release
|
Diffusion - drug diffuses through the coat at a rate determind by the nature of the drug and coating polymers
Polymer Erosion - polymer dissolution or disentanglement, e.g. beads coated with beeswax, glyceryl monostearate, or enteric coatings Osmosis - osmotic pump Film coating involves diffusion + osmosis |
|
|
Film Coating - Coating Polymers
|
Ethylcellulose
-Water insoluble -Most common, ideal material -Tasteless, odorless, resistant to alkali and can withstand dilute acids for limited periods -Excellent film former, stable in light/heat to 135 degrees Celsius -Often combined with soluble polymers, e.g. PEG, HPMC to provide aqueous channels |
|
|
Film Coating - Coating Polymers
|
-Methacrylate ester copolymers - from natural polymers --> tradename: eudragit RS/RL
-Water insoluble -Permeability dependent on number of hydrophilic groups in the polymer -Have very high molecular weights > 150,000 -Can also be formulated with water soluble polymers |
|
|
Film Coating - Coating Polymers
|
pH dependent water soluble polymers
-All contain carboxyl groups, e.g. insoluble at low pH but soluble at higher pH -Threshold pH (at which they dissolve rapidly) depends on number of carboxyl groups in the molecule -Cellulose acetate phthalate most common problem! Permeable to gastric juice & susceptible to hydrolytic breakdown on storage -Enteric coating - polymer doesn't dissolve in stomach -Principle - polymer doesn't dissolve in low pH --> dissolves in high pH |
|
|
Film Coating Equipment
|
-Coating pan (perforated)
-Fluid bed *Top spray *Bottom spray (Wurster) --> film is reliable --> coat is uniform *Tangential spray |
|
|
Pan Coating Equipment Suppliers
|
-Driam
-Glatt -Manesty (Thomas Engineering) -O'Hara -Vector Corporation |
|
|
Fluidized Bed Processes
|
Coating Particles
-Conventional To Spray -Wurster Bottom Spray -Rotor Tangential Spray |
|
|
Fluidized Bed Processes - Wurster Bottom Spray
|
Uniform Coating
|
|
|
Film Coating Dynamics
|
Droplet Formation
-Droplet formed by compressed air -Travel into primary evaporation medium Contact/coalescence -Spreading or retaining shape -Spray drying Evaporation Core penetration |
