It may have to do with a difference in the rate at which the two forms dissolve after administration, if given as a suspension or pill rather than a solution. The amorphous form probably dissolves faster than the crystal form because of greater intermolecular forces in the crystal.
Solubility depends on the formation of intermolecular hydrogen bonds between solvent molecules and the solute molecules. The crystalline form is more stable than the amorphous form and has a lower energy at the molecular level with stronger bonding (mostly ionic bonds) between molecules that require higher energy to break. So, higher solubility means higher dissolution rate and better bioavailability
In Simple terms .....Presence of water in terms of solvates ..... reduces the affinity of the drug towards water which in turn reduces the solubility and dissolution, thus hydrates are less soluble than its amorphous forms.
Yes, amorphous form of drug has the order of liquid or melt state of matter and lack the long range order of solid crystalline state. So, no energy is required to break the bonds during the dissolution process such in case of crystalline state. As a general, bioavailability is defined as rate and extent of drug absorption. The rapid release of drug leads to higher absorption rates. This can lead to a short Tmax. Also, C max will be higher for drugs suffered from higher metabolism in GIT by CYP3A4 enzyme because the rapid dissolution rate causes the escape of drug from exposure to metabolizing enzymes in the gut wall. So, higher bioavailability will be achieved for drugs with poor solubility in its crystalline state and higher metabolism in the gut wall if they are formulated as amorphous forms. Also, the higher bioavailability can be even greater if the formulation contains excipients having the dual role of dissolution enhancement and enzyme inhibitor like poloxamer with itraconazole.
But, in case of solvates like theophiline monohydrate the water molecule acts as abridge that links two molecules of theophylline which consequently requires the breakage during dissolution process.So, we can find that theophylline anhydrous is more soluble than its monohydrate form. However, in some cases, solvates may have higher solubility than anhydrous form.
I have just conducted formulation trials where spray-dried formulations, producing amorphous drug (midazolam) had very poor dissolution (poorer than the raw, crystalline, drug). Midazolam coground in a jet mill with other materials was still crystalline, but had a rapid dissolution profile (80% dissolved in 5-minutes). Why??
These are the solids which do not exhibit long-range order in any of the
three physical dimensions. There may be the existence of short-range order for amorphous solids. If you compare an amorphous phase with crystalline phase of a same drug, the amorphous phase always show higher free energy, enthalpy, and entropy than the crystalline one. To be simple and straight, the amorphous form has the small particle size so
more surface area and hence it is easily attacked by the solvent or the
moisture.
In amorphous form, inter molecular hydrogen bonding between amorphous form of drug and water is easier than crystalline form. Crystalline form is more rigid and intra-molecular force is more. Due to this reason, crystalline form will not form hydrogen bond easily and dissolution rate will be less.
we claim nanocompsites to be best in crystalline form but the solubility is mostly good in amorphous form so how we can justify our products solubility in crystalline form??
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