Lecture 16- Biopharmaceutics III Flashcards
Enhancing dissolution- lipid based formulations
Consists of drug dissolved in veg oil/triglycerides
High lipophilicity= facilitates drug absorption
Prescence of surfactant= enhanced absorption due to membrane induced permeation changes
Surfactants= stabilize the emulsion + protect droplets against aggregation
Co-solvents= increase the solubilization of incorporated drugs
Enhancing dissolution- size reduction technology
Surface area increases by decreasing particle size which results in higher dissolution rate
Reduction in particle size= accompanied by micronization - milling (impact and attrition), grinding + superficial fluid technology
Enhancing dissolution- functional polymer technology
Enhances the dissolution rate of poorly soluble drugs by avoiding the lattice energy of the drug
Fresh polymers are for exchange materials that interact with the ionizable molecules of the surrounding medium + exchange their mobile ions of equal charge with surrounding medium reversibly e.g. amber lite, duolite
Resultant complex; resinate= formulated as suspension, dry powder/tablet e.g codeine/ chlorpheniramine dual drug deliver
Enhancing dissolution- porous microparticle technology
Core technology applied as HDDS; hydrophobic drug delivery system - provide a larger surface area for increased dissolution rate
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Enhancing dissolution- hydrophilic solubilization
For poorly soluble drugs- uses a lecithin + gelatin-based water-soluble drug coating to improve dissolution + hydration
Coating forms= micelles which improve oral bioavailability of the insoluble drugs
Enhancing dissolution- controlled precipitation
Drug is dissolved in a water-miscible organic solvent + then dispersed into aqueous medium containing stabilisers
Solvent- dissolves in water and causes precipitation of the drug in the form of micro-crystals
Stabilizers= control particle growth + enhances the dissolution rate of poorly soluble drug due to large surface area, hydrophilized by the adsorbed stabilizer
Enhancing dissolution - inclusion complexes
Prepared with B-cyclodextrin + HP-B-CD; cyclic oliogosaccharide
Outer surface= hydrophilic
Inner surface= hydrophobic
Required quantity of B-CD is weighed + water added for consistency
Method-
To the mass, weighed quantity of the drug is added. The mixture is kneaded in a glass mortar for 1 hr and then completely dried in hot air oven at 60 oC for 2 hrs. The dried mass is then sieved
Enhancing dissolution- solid dispersions
Dispersion of one/more active ingredients in an inert carrier/matrix at solid state prepared by the fusion, solvent/melting solvent method
Carriers;
Sugars- dextrose, sorbitol, mannitol
Acids- citric, tartaric + succinic acid
Polymeric materials- PEG 4000, PEG 6000, HPMC
Enhancing dissolution- solid dispersions
Fusion method;
Mix drug + water-soluble carrier together.
Heat until the mixture melts.
Cool quickly (e.g., in an ice bath) to solidify.
For faster dissolution:
Pour the melt into a thin layer on a stainless-steel plate.
Cool using air or water flow underneath the plate.
Crush, pulverize, and sieve the final solid to get a fine powder.
Drug + carrier melted -> cooling/solidification -> crushed + sieved
Solvent evaporation method
Dissolve both the drug and carrier in a common solvent.
Evaporate the solvent to form a solid solution or mixed crystals.
Low temperature process → prevents thermal decomposition of drug or carrier.
Examples:
β-carotene + PVP
Griseofulvin + PVP
Tolbutamide + PVP
Drug + solid components -> dissolved in solvent -> solvent evaporated
Melting-solvent method- Drug is first dissolved in a solvent.
The drug solution is then mixed directly into the melted carrier (e.g., PEG-6000).
The mixture is then cooled to form a solid dosage form.
Used for liquid drugs like:
Methyl salicylate
Vitamin E
Clofibratell
Drug dissolved in solvent -> solution mixed with carrier melt
Enhancing dissolution- eutectics
A mixture of two or more substances that, at a specific composition, melts at the lowest possible temperature.
At this temperature, all phases crystallize together.
💧 Eutectics Enhance Dissolution Because:
a) Particle size reduction → increases surface area.
b) Increased solubility of the drug.
c) No aggregation or clumping of fine drug crystals.
d) Better wettability and dispersibility → carrier dissolves first, helping water contact the drug.
e) Drug crystallizes in a metastable form → higher solubility than stable crystals.
Intro
Oral administration- main route worldwide
Most newly developed drugs are hydrophobic
Aqueous solubility depends on;
- absorption rate
- drug permeability through lipophilic membranes
- bioavailability
