Akhmad Kharis Nugroho

Transdermal iontophoresis of rotigotine across human stratum corneum in vitro: Influence of pH and NaCl concentration

AbstractPurpose. The aim of this study was to characterize the influence of pH and NaCl concentration on the transdermal iontophoretic transport of the dopamine receptor agonist rotigotine across human stratum corneum (HSC). Methods. Rotigotine transport was studied in vitro in side by side diffusion cells according to the following protocol: 6 h of passive diffusion, 9 h of iontophoresis, and 5 h of passive diffusion. A current density of 0.5 mA cm−2 was used. The influence of donor phase pH (4, 5, and 6) and different concentrations of NaCl (0.07 and 0.14 M) on rotigotine iontophoretic flux were examined. The acceptor phase was phosphate-buffered saline (PBS) at pH 7.4 except in one series of experiments aimed to study the effects of rotigotine solubility on its iontophoretic transport. In this study, PBS at pH 6.2 was used. In separate studies, 14C-mannitol was used as a marker to determine the role of electro-osmosis during iontophoresis. Results. The estimated iontophoretic steady-state flux (Fluxss) of rotigotine was influenced by the pH of the donor solution. At a drug donor concentration of 0.5 mg ml−1, the iontophoretic flux was 30.0 ± 4.2 nmol cm−2 h−1 at pH 6 vs. 22.7 ± 5.5 nmol cm−2 h−1 at pH 5. However, when the donor concentration was increased to 1.4 mg ml−1, no significant difference in iontophoretic rotigotine transport was observed between pH 5 and 6. Increase of NaCl concentration from 0.07 M to 0.14 M resulted in a decrease of the rotigotine Fluxss from 22.7 ± 5.5 nmol cm−2 h−1 to 14.1 ± 4.9 nmol cm−2 h−1. The contribution of electro-osmosis was estimated less than 17%. Probably due to the lipophilic character of the drug, impeding the partitioning of rotigotine from HSC to the acceptor compartment, steady-state transport was not achieved during 9 h of iontophoresis. Conclusions. Both pH and NaCl concentration of the donor phase are crucial on the iontophoretic transport of rotigotine. Electro-repulsion is the main mechanism of the iontophoretic transport of rotigotine.

Compartmental Modeling of Transdermal Iontophoretic Transport II: In Vivo Model Derivation and Application

No HeadingPurpose.This study was aimed to develop a family of compartmental models to describe in a strictly quantitative manner the transdermal iontophoretic transport of drugs in vivo. The new models are based on previously proposed compartmental models for the transport in vitro.Methods.The novel in vivo model considers two separate models to describe the input into the systemic circulation: a) constant input and b) time-variant input. Analogous to the in vitro models, the in vivo models contain four parameters: 1) kinetic lag time (tL), 2) steady-state flux during iontophoresis (Jss), 3) skin release rate constant (KR), and 4) passive flux in the post-iontophoretic period (Jpas). The elimination from the systemic circulation is described by a) the one-compartment and b) the two-compartment pharmacokinetic models. The models were applied to characterize the observed plasma concentration vs. time data following single-dose iontophoretic delivery of growth hormone-releasing factor (GRF) and R-apomorphine. Moreover, the models were also used to simulate the observed plasma concentration vs. time profiles following a two-dose transdermal iontophoretic administration of alniditan.Results.The time-variant input models were superior to the constant input models and appropriately converged to the observed data of GRF and R-apomorphine allowing the estimation of Jss, KR, and Jpas. In most cases, the values of tL were negligible. The estimated Jss and the in vivo flux profiles of GRF and R-apomorphine were similar to those obtained using the deconvolution method. The two-dose iontophoretic transport of alniditan was properly simulated using the proposed time-variant input model indicating the utility of the model to predict and to simulate the drug transport by a multiple-dose iontophoresis. Moreover, the use of the compartmental modeling approach to derive an in vitro-in vivo correlation for R-apomorphine was demonstrated. This approach was also used to identify the optimum in vitro model that closely mimics the in vivo iontophoretic transport of R-apomorphine.Conclusions.The developed in vivo models demonstrate their consistency and capability to describe the in vivo iontophoretic drug transport. This compartmental modeling approach provides a scientific basis to examine in vitro-in vivo correlations of drug transport by iontophoresis.

Optimization of Self-nanoemulsifying Drug Delivery System for Pterostilbene

An UV spectrophotometric area under curve method was developed for the estimation of Levofloxacin Hemihydrate in its mono component tablets. The spectrophotometric method for estimation employed Area under curve method for analysis using 0.1M Sodium Hydroxide as solvent for the drug Levofloxacin Hemihydrate at the wavelength range of 285-295nm. Levofloxacin Hemihydrate obeys Beer’s law in concentration range 10-50µg/ml. The recovery studies ascertained accuracy of the proposed method and the result validated according to ICH guideline. Results of analysis have been valid statistically by recovery studies. The method was successfully for evaluation of Levofloxacin Hemihydrate in tablet dosage form without the interference of common excipients.

Optimization Direct Compression's Co-Processed Excipient Microcrystalline Cellulose PH 102 and Povidone ® K 30

The objective of the present study was to develop filler-binder co-processed excipient (CPE) from MCC PH 102 and Povidone® K 30 combination. The mixture was varied and co-processed by spray drying technique. Optimum proportion was determined by testing the flow ability and compressibility expressed in Tapping Index (T.I) and hardness, respectively. The test result indicates that the flow ability was fluctuating in different CPE proportions, while compressibility improved with the increase in proportion of Povidone ® K 30. Optimum proportion was reached at 71 % MCC PH 102 and 29 % Povidone ® K 30, with the values of T.I and hardness of 16,22 ± 0,39 % and 7,61 ± 0,12 kg, respectively. Optimum CPE generates tablets of paracetamol model drug that meet the USP requirements of tablet dosage, which include hardness, friability, disintegration time, and dissolution.