Salt formation is an acid – base reaction involving either a proton- transfer or neutralization reaction and is therefore controlled by factors influencing such reactions.
One of the simplest methods of preparing oral sustained release dosage forms is by using poorly soluble derivatives of a drug. Tannate salt is FDA approved salt and 0.88 percent is use through 1974. Tannic acid also known as gallotannic acid, gallotannin, glycerite or tannin. It is typically produced from Turkish or Chinese nutgall and has a complex, non-uniform chemistry. Antihistamines in the form of their tannate salts can be prepared by different approaches. Marketed Products of tannate are available.
One of the simplest methods of preparing oral sustained release dosage forms is by using poorly soluble derivatives of a drug so that the rate of availability of drug for absorption can be monitored precisely and easily. Tannate salt is FDA approved salt and 0.88 percent is use through 1974.1 Tannic acid was reported to yield non-toxic and stable derivatives with amines, having prolonged action. Tannins are water – soluble phenolic metabolites of plants. Physicochemicaly, tannins are complex polymers, which can be classified as: Condensed tannins and Hydrolysable tannins. Hydrolysable tannins or tannic acid are composed of gallic acid or its condensation product ellagic acid esterified to the hydroxyl groups of glucose. Each hydrolysable tannin molecule is usually composed of a core D – glucose and 6 to 9 galloyl groups.2 In nature, there is an abundance of mono and di-galloyl esters of glucose with a molecular weight of about 900. These are not considered to be tannins. At least 3 hydroxyl groups of the glucose must be esterified to exhibit a sufficiently strong binding capacity to be classified as tannin. 1 Tannic acid also known as gallotannic acid, gallotannin, glycerite or tannin having decomposition point 210-215 C and is highly soluble in water and alcohols. Tannic acid is commercially available with water content of about 10% by weight. Its Molecular formula is and a molecular weight of about 1700. It is typically produced from Turkish or Chinese nutgall and has a complex, non-uniform chemistry.2,3 Antihistamine compound in the form of their free bases as well as their salts, e.g. - hydrochloride, maleate etc. are well known. 2
Synonyms - Gallotannic acid; Gallotannin; Galloylglucose; Glycerite;
Molecular Formula - C76H52O46
Molecular Weight - 1700
Melting point - 218°C
Water solubility - 1g/ 0.35 ml
Approaches for preparation of tannate salt of antihistamines:
Antihistamines in the form of their tannate salts can be prepared by following a number of different procedures.2
In the first approach, the free base, e.g. diphenhydramine, etc. is reacted with tannic acid in the presence of a volatile solvent, isopropanol.
A second approach to prepare the antihistamine tannate is to contact the free base form of the drug with tannic acid in the presence of water for a suitable period of time and at a maximum temperature. The antihistamine tannate salt needs to be isolated and purified by freeze drying and then subsequently introduced into pharmaceutically effective dosage forms.
A third and better approach to prepare the antihistamines, in this an aqueous solution or the powder form of the drug is reacted with tannic acid mixture in liquid or powder form. The tannate salt can be directly incorporated into suitable pharmaceutically effective dosage forms without being subjected to high temperatures that can produce undesirable decomposition products.5
The tannate salt of the antihistamine can also be prepared without the use of organic solvents, which would be desirable from an environmental standpoint. This also allows one to eliminate organic solvents as a possible contaminant in the final dosage product.
Many antihistamine tannates are heat sensitive and therefore undergo decomposition quite readily upon prolonged exposures to temperatures as low as 50 C. The antihistamines in the form of its free base is contacted with tannic acid in the presence of water at a maximum temperature which will not cause decomposition of tannate to an extent of greater than about 5 wt%, based on the weight of the antihistamine tannate, for a period of about 5 minutes to 4 hours at said maximum temperature. Diphenhydramine tannate prepared by reacting diphenhydramine freebase at temperature of about 20-wt% water.6
Marketed Products and study on Tannate salt:
Sustain release tablet of diethylcarbamazine was prepared using tannic acid.7 Antihistaminic tannate compositions invented with diphenhydramine tannate as the lone active ingredient2 and also DYTAN is available for oral administration as a chewable tablet of diphenhydramine tannate.
A well designed salt selection and optimization study provides a sound base on which to build a rapid and economical product development program. Salt selection involved multiple functions; there is no one size fits all approach. Tannate salt is one of the pharmaceutical salt for which conclude through review that is good stable, easily and economically approachable and feasible for formulating simple sustained-release formulations.