Formulation, Characterization and Evaluation of Controlled Released Semi Solid Dosage Forms for Transdermal Drug Delivery from Various Extracts of Ephedra herba, Hedera helix L and Thymus serpyllum L.

Abstract

Asthma is reversible inflammatory airway disorder in which several cells and cellular elements plays greater role. In Pakistan this disease is very prevalent. No remedy is available for asthma. In allopathic medicines, generally corticosteroids are used to treat asthma. Many herbal remedies are available worldwide which gave very good results but their scientific evaluation and validation in asthma is almost nil. Three herbal plants namely Ephedra, Hedera helix L. and Thymus serpyllum L. are found to be very popular by local people as remedy for asthma in Pakistan. Mostly used as herbal tea and paste for inflammation. In the current research study, these three plants were selected and their extracts were prepared by hydroalcholic and steam distillation process. These extracts were phytochemically screened. The antioxidant activities and IC50 values were measured. The free radical scavenging activity of Ephedra, was 90.08% ± 1.37, Thymus serpyllum L. 80.9% ± 0.5 and Hedera helix L. 78% ± 0.3. Extracts were qualitatively and quantitatively analyzed by TLC, HPLC and UV-spectrometer. The extracts were selected for three topical formulations containing microemulsion, gel and ointment. In-vitro diffusion (flux) was checked by Franz diffusion cells. Effect of dialysis cellulose membrane and natural rabbit skin on the release of medicaments was also analyzed by using Franz cells. The flux, Jss (µg/cm2/h) for microemulsion, gel and ointment of Ephedra on dialysis cellulose membrane and natural rabbit skin were 1.346, 0.79, 0.656 and 0.70, 0.76, 0.641 respectively, For Hedera helix.L. The flux for microemulsion, gel and ointment on dialysis cellulose membrane and natural rabbit skin were 5.10, 4.02, 2.80 and 4.10, 3.10, 1.40 respectively. For Thymus serpyllum L. the flux for microemulsion, gel and ointment on dialysis cellulose membrane and natural rabbit skin were 7.10, 5.02, 3.80 and 6.10, 4.12, 2.40 respectively. The stable formulations were also selected for further characterization including rheological studies, FTIR, XRD, Zeta size and Zeta potential. It was observed that all preparations were significant staistically; with little variation from one another. For in-vivo studies, HPLC analytical methods were developed and validated under ICH guidelines. The in-vivo studies were performed on rabbits. The Pharmacokinetic parameters i.e. Cmax (µg/ml), Tmax (h), AUC (µg/ml) and MRT (h) were analyzed. For topical microemulsion and gel, Cmax were 27.53 µg/ml, 39.12 µg / ml of pseudoephedrine, 70.22 µg /ml, 75.26 µg /ml of hederacoside C and 35.33 µg /ml, 42.13 µg /ml of thymol respectively. For marketed oral syrup, Cmax values were 251.11 µg /ml, of pseudoephedrine 90.11 µg/ ml, of hederacoside C and 95.23 µg/ml of thymol. Maximum plasma concentration for optimized microemulsion and gel was 6 hours for pseudoephedrine 2 hours for hederacoside C and 3 hours for thymol (same values for both formulations). Plasma concentrations of marketed oral syrups were 2 hours, for pseudoephedrine 1 hour for hederacoside C and 2.0 hours for thymol. Area under curves for microemulsion and gel were 418.76 µg/ml/h, 529.81 µg /ml /h, for pseudoephedrine 492.83 µg/ml/h, 613.10 µg /ml /h for hederacoside C and 396.72 µg /ml/h, 498.44 µg /ml /h, for thymol respectively. Areas under curve for oral syrup were 985.35µg/ml/h, 329.58 µg/ ml /h, and 277.96 µg/ml/h for Pseudoephedrine, hederacoside C and thymol. Mean residence time for microemulsion and gel were 14.81 hours, 12.06 hours, 10.03 hours, 12.95 hours and 12.15 hours, 11.36 hours for Pseudoephedrine, hederacoside C.and thymol respectively. Mean residence time for commercially available syrup were 3.85 hours, 4.05 hours and 9.41 hours for Pseudoephedrine, hederacoside C.and thymol Results of all pharmacokinetic parameters were significant (P < 0.05). It is concluded that topical herbal formulations have greater bioavailability as compared to conventional syrups. Thus It has proved that transdermal formulations prepared using these plants had good bioavailability properties in blood plasma. It is further concluded that these traditional herbal formulations were successfully developed, characterized in formulated in to enhanced transdermal drug delivery systems. The sustainability was improved from 6 hours for all formulation to 24 hours.