Preliminary experiments for selection of the most suitable mucoadhesive in situ forming gelling system of DMH

Before conduction of the preliminary studies, all experimental procedures were approved by the ethical committee of faculty of pharmacy, Ain Shams University (approval number ASU 94), and were conducted according to the guidelines and regulations dictated by this protocol.

Formulations containing different concentrations of the thermosensitive polymers P407 and P188 were prepared using the cold method^{17, 23, 24}. The composition of the prepared formulations is shown in Table (​(1).1). Briefly, the in situ gelling formulations were prepared by dissolving the drug (with or without PEG 400) in phosphate buffer saline (PBS) pH 7.4 at room temperature followed by sonication (Transsonic, model TI-H 5, Germany). The thermosensitive polymers P407 and P188 were then added to the buffer in cold water bath on a magnetic stirrer (Jenway, England) followed by storage in the refrigerator with periodic stirring till homogenous formulations are obtained. In order to preliminary assess the effect of drug amount on the formulation of the in situ forming gelling system; variation of the amount of drug from 50 mg to 75 mg and 100 mg was carried out as shown in Table (​(1).1). The amount of incorporated DMH was then escalated to 200 mg.

Composition of the prepared in situ gelling systems of dimenhydrinate and their gelation temperature.

^*PEG 400 (0.5 ml) was included in all formulae except F1-F4.

^**Not determined since the formulae showed precipitation of DMH.

HA: Sodium hylauronate.

CS: Chitosan.

After reaching DMH in situ gel formulae which undergo gelation at the physiological temperature, preliminary experiments were conducted for the incorporation of mucoadhesive using either chitosan (CS) or hyaluronic acid (HA) as also shown in Table (​(1).1). The mucoadhesive substances were added to the in situ gelling formulations showing acceptable gelation temperature.

For mucoadhesive formulations prepared using CS, the chitosan solutions were prepared by dissolving it in 0.1 N acetic acid. CS solutions were then added to the dissolved drug with PEG 400 in the buffer PBS (pH 7.4) at room temperature with sonication, to achieve different final CS concentrations. The addition of P407 and P188 then followed in cold water bath. The solutions were stored in the refrigerator with periodic stirring till homogenous.

For mucoadhesive formulations prepared using HA, formulae were prepared by dissolving the drug, PEG 400 and different concentrations of HA in the buffer PBS (pH 7.4) at room temperature with the aid of sonication, according to the concentrations shown in Table (​(1).1). After the mucoadhesive polymer HA was dissolved, the poloxomer P407 and P188 were added to the formulations. The formulations were left in a cold water bath with magnetic stirring till complete dissolution of poloxamer, followed by refrigeration storage with periodic stirring.