What are different strategies to prepare immediate relase dosage form with BCS CLass II drugs?
direct compression
dry-,wet,melt-granulation
solid dispersion
freeze drying or lyophilization
The oral bioavailability of BCS class II drugs can be either dissolution rate-limited (IIa) or solubility-limited (IIb) as explained in this publication [Butler J.M., Dressman J.B. - The developability classification system: application of biopharmaceutics concepts to formulation development. - Journal of Pharmaceutical Sciences, 99(12), 4940-4954, 2010]
The formulation strategy to improve oral bioavailability can be:
- for Class IIa: particle size reduction to increase the surface of contact between the drug and dissolution medium or addition of surfactant to facilitate the wetting of the drug.
- for Class IIb: solid solution (mostly by Hot-Melt Extrusion or Spray-Congealing) and lipid-based formulations (Self Emulsifying Drug Delivery Systems) are the most common techniques to avoid the dissolution step of the crystalline drug in the gastointestinal tract (by the amorphization of the drug in the solid solution or dissolution of the drug in the lipid-based formulations).
Vincent Jannin Thanks for that! I just managed to find and read the abstract. I tried to get an access to the paper thru my institution, but the latter maybe not subscribed to this journal.
I want to know, at what particle size, the class 2 drug can possibly becomes a class 2A or 2B, in other words, what are the ranges of particle size that sub-classify class 2 drugs into class 2A and 2B?
And why?
I mean, If for instance (assumably speaking, because I still don't know), if the larger particle size of a drug has a dissolution-limited process rather than a solubility-limited process (hence, a kinetic/physical process 'rate' is more affected than the chemical process 'extent'), then, why a larger particle size can hinder the rate but not the extent of dissolution? Or, if not, why then the opposite scenario is true?
Does the answer for the latter Q has to do with different ionization/acidity of class 2 drugs? and subsequently on their solubility!
I'm a bit confused here, what is the relationship that this DCS found between particle size, ionization, and dissolution rate vs solubility (saturated or intrinsic ones) for the class 2 drugs (high permeability low solubility drugs)?
I'll really appreciate if you can help me to find an exit for this puzzle!!
Thanks in advance!!
Dear Dahmash
If the particle sizes of a powder are too-large, the solvent cannot penetrate freely into the powder. In other word, the contact area between of the solvent and the solute is small. On the other hand, if the sizes of the particles are too-small, the contact area between of the solvent and the solute is high enough to penetration of the solvent into the solute. So the particles are going to the solution. The Noyes-Whitney equation, explains this relationship of particle size and dissolution rate:
dC/dt=Dissolution rate= DS(Cs-Ct)/Vh
in which:
- D: Diffusion coefficient
- S: Surface area of the solid exposed (Contact area)
- V: Volume
- h: Thickness of diffusion layer
- C: Concentration
For the drugs that dissolution rate is a problem, reduction is size is one of the answers. For the drugs that solubility is a problem, it means that the solvent has not affinity and attraction to the drug. The emulsification, change in salt of drug, change in crystallinity can help.
Liquisolid technique and then self-emulsifying systems for solid dosage forms, can be a good way to increase the dissolution rate and solubility of the drug.
Thanks Saleh! It’s good that you brought the N&W equation to the discussion. And thanks for the latter clarification. things are much clearer now!
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