Aspirin is a known NSAIDs drug which has the longest product life cycle. Aspirin is very sensitive to moisture content so it is manufactured by direct compression technique. However, direct compression of aspirin result in the formation of amorphous aspirin which has a higher kinetic energy that can lead to stability problem particularly, hydrolysis of aspirin to give acetic acid and salicylic acid (keratolytic agent). So, a bad smell of acetic acid from aspirin tablets indicates the bad storage of aspirin tablet. Also, a coated tablet of aspirin with needles on its surface indicates the hydrolysis of tablet. in addition, residual amounts of salycilic acid in aspirin tablet is a required test in USP. The HPLC method must be used to diffrentiate between ASA and SA (difference in polarity). Dissolution test is performed and analysis of withdrawn samples can be a useful tool in determining if aspirin is dissolved or hydrolyzed. So, UV spectroscopic method can not be able to do this task as ASA and SA have the same chromophore and consequently the same absorbance. I think that ASA is the absorbed form of aspirin not SA. Because SA is more polar than ASA that leads to poor or no absorption from GIT. Mesalamine may support this thought as dimer of 5 amino-salycilic acid leads to a significant increase in the hydrophilic character that prevent its absorption. This ensures delivery of drug to colon to treat Ulcerative colitis. Acetyl group in aspirin lend it an optimum partition cofficient for transcellular absorption.

The stated method in the USP 36 to monitor the enteric coated aspirin dissolution based on the UV spectroscopy to monitor the release of aspirin in the acidic medium for 2 hrs at wavelength 285 nm with limit not excedding10% and then for 1 hr in the buffer stage at different wavelength 260 nm. this method sufficient to be sure that there is no release of aspirin in the acid media. in addition, u can also analyse the free salicylic acid by HPLC.

Salicylic acid, the active metabolite of aspirin. Salicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is poorly soluble in the acidic conditions of the stomach. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed rapidly there, which in turn allows more of the salicylate to dissolve. About 50–80% of salicylate in the blood is bound to albumin protein, while the rest remains in the active, ionized state.As much as 80% of therapeutic doses of salicylic acid is metabolized in the liver.

Lets roughly assume that half of the aspirin is dissolved and half is hydrolyzed in the polymer matrix but since it is coated, drug is still in the polymer matrix and has not diffused out yet. So the hydrolyzed part which is salicylic acid will dissolve again in the intestinal and generate some more proton. Is it right? So the question here is can we assume that molar concentration of aspirin is same with produced proton because of dissolution plus hydrolysis.

No, if you mean the hydrolyzed part (50%) which is then further dissolved. This is due to that the dissolution process does not mean the hydrolysis of drug, as general rule, but dissolution, a kinetic process, means the presence of drug in the free molecular form that has the order of liquid or melt like structure, not the order of solid state. The molar concentration, in this case, will be the half of the dose present in the coated tablet according to your assumption.

Also, sink condition achieved by large absorptive surface area of small in the intestine ensures the flux of drug from intestinal lumen to blood side according to concentration gradient. So, the molar concentration of ASA will be changed with time (decrease) due to absorption process.

Lets explain some points regarding aspirin absorption :

once aspirin passes through the stomach into the small intestine,

the pH rises to 5.5-6.5. At this pH most of the aspirin deprotonates,

becomes ionized, and becomes very soluble. However, there is still a

couple of percent of neutral aspirin which can passively move through the

membrane and then be absorbed via the portal vein into the blood from

whence it goes directly to the liver. (The charged/ionized form cannot

readily pass through the membrane.) Since this movement across the

membrane removes neutral aspirin from the intestine, the chemical

equilibrium between the neutral and ionized form of aspirin is changed and

some of the ionized form will bind a proton to reestablish the

equilibrium. This goes on repeatedly until it's all absorbed. In effect,

the absorption of the neutral form drives the chemistry to make more

neutral form in the intestine which gets absorbed, which makes more

neutral form and on and on.In addition, aspirin absorbed as ASA and then hydrolyzed in the body after absorption not in the intestine to salicyilc acid which is the active metabolite of the aspirin.Therefore if your aspirin hydrolysed in the matrix its concentration will decrease in the intestine and as a result in the blood.

Salisylic acid may also absorbed from the intesine but with different mechanism so we can't be sure about the amount of the drug that could reach the blood in this case.

Will it be the same if the aspirin not hydrolysed or not. Your assumption should be evaluated by practical work.

Thanks, answers are quite helpful for me. Finally can you please suggest me a nice book or document related with aspirin chemistry, functional groups, effect of these groups on polarity, solubility etc. There are so many, but most of them are so superficial.

Hi,

According to my knowledge, if aspirin is well formulated and followed for long-term stability study with no significant change, then the percentage of free S.A. should not exceed 3% according to USP & BP whether plain or enteric coated tablets. In the dissolution test which a simulation of GIT condition , we will measure the A.S.A. released from the dosage form and not the S.A. which means that A.S.A. is stable enough to be released and absorbed (note that we use A.S.A. reference std for comparison using HPLC not U.V. ). Moreover, A.S.A degradation depends not only on moisture content , but also on temperature rise which accelerates degradation in shorter time, while moisture alone if present in the formula causes gradual hydrolysis which can be detected on long-term storage. After absorption, the A.S.A will undergo hydrolysis to S.A which has the pharmacological activity.

Can aspirin absorb from alkaline media

Yes, aspirin will be completely ionized in the pH of intestine. This make it more water soluble. But there is micro-environmental pH, on the outer wall of enterocytes, which is lower than the pH of intestine. This ensure conversion of aspirin from ionized state into non ionized state which is the absorbed form of drug. So, aspirin can be formulated with Al(OH)3 as a basic media to enhance the solubility of aspirin in the diffusion layer. But when aspirin goes out the diffusion layer, it will form a preciptate with a higher surface area. This technique can enhance the dissolution rate of aspirin.

Maybe this would be interesting for you:

Acetylsalicylic Acid

Karsten Schrör

ISBN: 978-3-527-32109-4