Based on solubility, absorption ratio, toxicity and also it should not degrade by bile acid or strong acid in the stomach

Agree with Prakash.

In short good bioavailability is the keypoint

compounds following Lipinski's rule of five shows good oral bio-availability.

For a compound to reach a tissue, it usually must be taken into the bloodstream - often via mucous surfaces like the digestive tract (intestinal absorption) - before being taken up by the target cells. Factors such as poor compound solubility, gastric emptying time, intestinal transit time, chemical instability in the stomach, and inability to permeate the intestinal wall can all reduce the extent to which a drug is absorbed after oral administration. Absorption critically determines the compound's bioavailability. Drugs that absorb poorly when taken orally must be administered in some less desirable way, like intravenously or by inhalation (e.g. zanamivir). Routes of administration is an important consideration.

Thanks Amir Haider, My synthesized compounds are now in HCl salt form, and easily soluble in water, any other suggestions???

Dr.Satish,

In fact the hydrochloride salt is selected 50% of the time when chemists look for an acceptable salt. The hydrochloride is a preferred choice because chloride does not have any activity of its own, unlike bromide, nitrate and others. Hydrochloric acid is a very significant acid in the stomach. By salt exchange hydrochlorides are formed to some extent no matter what the counter ion of an API is in the pharmaceutical product. Hydrochloric acid is a strong mineral acid strong enough to quantitatively protonate even weak bases. Hydrochlorides characteristically are substantially more soluble than the free bases used to make them, so the hydrochloride typically improves the bioavailability.

Lipinski's rule of five is the answer

Poor absorption or permeation are more likely when there are:

1) More than 5 H-bond donors

2) The molecular weight is over 500

3) The CLog P is over 5 (or MLOGP is over 4.15)

4) The sum of N's and O's is over 10

All parameters are centered around number 5

Also to enahnce absorption and minimize ionization use the HCl salt for basic compounds and potassium or sodium salts for acidic compounds. The later mostly enhance water solubility allowing the formulation of injectable dosage forms.

In addition to the answers given earlier, you should consider first-pass metabolism, which can decrease/eliminate bioavailability.

Sir Ashraf Abadi,

I salute you on your depth study,you have also clear some my concept too.

Regards

Amir

In general, biologic compounds such as antibodies (e.g. Rituxan, Herceptin), cytokines (e.g. Neupogen, Neulasta, Epogen), fusion proteins, are not bioavailable when administered orally. That is because they are destroyed by the enzymes of the GI tract. The structure function relationships have failed to offer high predictive scores. Therefore, most scientists in developmental therapeutics, will administer the drug powder via gavage and then check blood levels. The difficulty is not in finding drugs that can be administered orally but rater to find drugs that are suitable for parenteral administration.

Agree with SIr. Ashraf Abadi, however, the point raised by Prof. Fatih Uckun is very important as well.