| Coleus forskohlii (Willd) Briq. is an important indigenous medicinal plant. The main active ingredients of Coleus Forskohlii-forskolin or isoforskolin can directly activate adenylate cyclase and thus increases intracellular cAMP levels greatly. The main pharmacological effects of forskolin or isoforskolin such as strengthening the heart, reducing blood pressure, expanding the bronchus, inhibiting tumor, promoting adipolysis and glycogenolysis, and preventing platelet aggregation are mediated by the increase of cAMP. In this paper, the physicochemical properties and intestinal absorption characteristics of forskolin and isoforskolin were investigated. Based on the results of these studies, a dispersible tablet of the extract of C. forskohlii was developed.The solubility, lipid/water partition coefficient and stability of forskolin and isoforskolin were investigated using HPLC as an analytical method. The solubility of isoforskolin and forskolin was about 110μg/mL and 10μg/mL, respectively. The lipid/water partition coefficient (log P6.5) was 2.63 for isoforskolin and 3.06 for forskolin. Forskolin was unstable in the pH range of 7.5～9.5. The degradation product was isoforskolin. The degradation rate increased with the increase of pH value. However, isoforskolin remained stable in these conditions. Isoforskolin had better drug-like properties than forskolin.Intestinal absorption characteristics was investigated using in situ single pass perfusion method. The results showed that forskolin could be absorbed in the whole intestinal segments. The effective permeability (Peff) was the highest in the duodenum compared to other intestinal segments. The main mechanism of intestinal absorption was passive diffusion, as well as a saturable transport process in the duodenum and colon. Unstirred water layer had no obvious impact on the absorption. Addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across rat jejunum. There was no statistical difference in Peff values between isoforskolin and forskolin in rat jejunum. The absorbed fractions of dissolved forskolin and isoforskolin after oral administration in human were estimated to be 100% calculated from rat Peff values. In conclusion, dissolved forskolin and isoforskolin could be absorbed readily in the intestine. It was of high importance to come up with innovative strategies to increase the solubility and dissolution rate to avoid losing an interesting drug candidate.The extract of C. forskohlii (ECF) containing 70.5% of isoforskolin was prepared by macroporous resin adsorption followed by elution, separation and purification procedures. Dispersible tablets of ECF was prepared by direct compression method, using lactose complex as filler, PVPP as disintegrant, and surfactant as solubilizer. The content of ECF in the tablet was 2%. The appearance, hardness, frangibility, dose uniformity, disintegration time, dissolution rate and uniformity of dispersion of ECF tablets were investigated. The results complied with the requirements of Chinese Pharmacopoeia 2010. Isoforkolin could be released promptly from ECF tablets, cumulative dissolution was> 96% within 20 min.In conclusion, the drug likeness of isoforskohlin is better than that of forskohlin, which provides a broader selection in administration route and formulation. The ECF dispersible tablet prepared has a significant advantage of high disintegration and dissolution rate. It is expected to be a modern Chinese medicine preparation with definite constituents, good effect, and high quality. |
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