Development Of Transdermal Therapeutic System Research Articles

Formulation development and characterization of Lecarnidipine hydrochloride niosomal transdermal patches

The bioavailability of Lercanidipine Hydrochloride (LCP) is about 44% and half-life of the drug is about 4.6 hours. LCP due to its low therapeutic dose range of 2.5 to 20mg and substantial biotransformation in liver becomes it ideal molecule in development of transdermal therapeutic system. The primary objective of the present research work was to develop Niosomal transdermal patch (NP) of Lecarnidipine. The LCP nanoparticles were prepared by solvent evaporation method and the optimized Nanoparticles formulation has shown 225nm particle size with a polydispersity index (PDI) of 0.120. LCP patches were prepared by incorporating nanoparticles dispersion, using varying concentrations of polymers HPMC E5, HPMC 5cps, HPMC 15cps, Carbopol 734 and Sodium alginate using solvent casting techniques and further optimized by central composite design(CCD) the effect of polymer on the various physico-chemical characteristics and in-vitro drug release studies, ex-vivo skin permeation studies is studied. On the basis of in-vitro drug release and ex-vivo skin permeation studies, the formulation containing (HPMC 15cps and HPMC 5cps) has shown sustained and extended drug release over a period of 24 hrs.
 Keywords: Lecarnidipine; Niosomes; Transdermal patch; Central composite Design, Controlled release; Bioavailability etc.

Study of Polymer Nanofilms Using for High-Throughput Screening in the Development of Transdermal Therapeutic System.

We investigated polymer nanofilm (PNF) for use in high-throughput screening (HTS) to promote the development of transdermal therapeutic systems (TTS). The drug permeability of PNF with a 1 : 1 weight mix ratio of poly(L-lactic acid) (PLLA) and poly(methylhydrosiloxane) (PMHS) (PLLA/PMHS (1/1) PNF) and Strat-M® of the transdermal diffusion test membrane, was evaluated using 12 kinds of drugs with the logarithmic value of n-octanol/water partition coefficients of -4.70 to 3.86. The lag time of PLLA/PMHS (1/1) PNF made via polymer alloying was significantly shorter than that of Strat-M® for 10 drug types, and the formation of a highly diffusible PMHS-rich phase accompanying the formation of a sea-island structure was suggested as a contributing factor. Additionally, a high correlation was confirmed between the measured value for the logarithm of the apparent permeability coefficient of PLLA/PMHS (1/1) PNF and the literature values for the logarithm of the apparent permeability coefficient of human skin (r = 0.929). This study shows that PLLA/PMHS (1/1) PNF can reliably predict drug permeability in human skin and can potentially be used in HTS for developing TTS.

The Combined Use of Synthetic and Biological Test Systems in the Development of Transdermal Therapeutic Systems

The Combined Use of Synthetic and Biological Test Systems in the Development of Transdermal Therapeutic Systems

Study of the Drug Diffusion Through Polymeric Membranes

We present the studies carried out on the transport properties of some membranes obtained from synthetic polymers: polyurethane and ethylene-vinyl acetate copolymer, for use in the development of transdermal therapeutic systems with limiting membranes of speed. The properties of drug active substances transport through membranes were highlighted by performing studies with a diffusion cell. Experimental drug active substances were paracetamol and tetracycline. The experimental data obtained was processed using a general mathematical model for drug release from non-porous, non-swellable transdermal devices, which starts from Fick�s second law and has terms that also take into account the possibility of retaining the drug in the membrane polymer. Even though the mathematical model does not take into account neither the swelling phenomenon nor the possibility of membrane erosion, a good agreement between model and experimental data was obtained. The values of effective diffusion coefficients of drug in the polymeric membranes were also determined.

Investigation of in vitro permeability of ketorolac tromethamine through a semipermeable membrane in the process of pharmaceutical development of transdermal therapeutic system

Investigation of in vitro permeability of ketorolac tromethamine through a semipermeable membrane in the process of pharmaceutical development of transdermal therapeutic system

Impact of Humidity on In Vitro Human Skin Permeation Experiments for Predicting In Vivo Permeability

In vitro skin permeation studies have been commonly conducted to predict in vivo permeability for the development of transdermal therapeutic systems (TTSs). We clarified the impact of humidity on in vitro human skin permeation of two TTSs having different breathability and then elucidated the predictability of in vivo permeability based on in vitro experimental data. Nicotinell(®) TTS(®) 20 and Frandol(®) tape 40mg were used as model TTSs in this study. The in vitro human skin permeation experiments were conducted under humidity levels similar to those used in clinical trials (approximately 50%) as well as under higher humidity levels (approximately 95%). The skin permeability values of drugs at 95% humidity were higher than those at 50% humidity. The time profiles of the human plasma concentrations after TTS application fitted well with the clinical data when predicted based on the in vitro permeation parameters at 50% humidity. On the other hand, those profiles predicted based on the parameters at 95% humidity were overestimated. The impact of humidity was higher for the more breathable TTS; Frandol(®) tape 40mg. These results show that in vitro human skin permeation experiments should be investigated under realistic clinical humidity levels especially for breathable TTSs.

Transdermal delivery of trazodone hydrochloride from acrylic films prepared from aqueous latex

Trazodone hydrochloride has not been previously investigated and reported for potential administration through transdermal route. Therefore, the present investigation was carried out to study the effect of polymeric composition, drug content and plasticizer on the permeation of trazodone hydrochloride across the mouse epidermis for the development of transdermal therapeutic system. The pseudolatex films with different combination of polymers, plasticizer and drug were prepared from aqueous colloidal polymer dispersions. The polymers used were Eudragit RL100 and RS100. Triethylcitrate was used as plasticizer. The in vitro release and skin permeation through mouse epidermis from the prepared films were studied using Keshary-Chien diffusion cell. The in vitro drug release increased with increasing amount of Eudragit RL100 in the film. It was observed that the maximum skin permeability was attained at a loading dose of 10% w/w in the film. The in vitro flux decreased gradually at higher concentration up to 13% w/w. The present study has demonstrated the potential of the fabricated pseudolatex transdermal films for sustained release of trazodone hydrochloride. The concentration of triethylcitrate in the film markedly affected the skin permeation properties of trazodone hydrochloride.

Flow-through system effects on in vitro analysis of transdermal systems.

The development of transdermal therapeutic systems (TTS) often involves in vitro evaluation of formulations and prototypes using flow-through diffusion cells. The apparent flux obtained from such methodologies does not accurately represent the actual (intrinsic) permeation of the compound through the skin. Flow-through system parameters, i.e., fraction collector tube volume, receiver cell volume, flow rate, and sampling interval, modify the flux yielding an apparent flux. Both finite-dose flux profiles and infinite-dose diffusional lag times are modified by these parameters. In this study, a transfer function is derived which describes the effect of these parameters. The intrinsic flux is calculated from apparent flux data using the transfer function and experimental flow-through system parameters. This allows the calculation of permeant flux profiles devoid of modification by the experimental methodology.

Development of Transdermal Therapeutic Systems

(1983). Development of Transdermal Therapeutic Systems. Drug Development and Industrial Pharmacy: Vol. 9, No. 4, pp. 579-603.