Pharmacokinetics of a Transdermal Nicotine Patch Compared to Nicotine Gum

Abstract

A new transdermal nicotine delivery system (TBS-NCT)was investigated in laboratory and clinical studies with healthy cigarette smokers. Plasma nicotine concentration time profiles were characterized during and after 24-hr application of three doses of TBS-NCT and during and after a 6-hr regimen of nicotine polacrilex gum. Pharmacokinetic analysis revealed dose-related plasma concentrations for transdermal treatments, bracketing the concentrations obtained from nicotine gum. The TBS-NCT system was also well tolerated during a subsequent 4-week open trial and demonstrated a 40% success rate for smoking cessation during the course of the trial. Overall, the TBS-NCT system appears suitable for once-daily application as an aid in smoking cessation treatments.     

Transdermal Nicotine Delivery Systems: Multi-institutional Cooperative Bioequivalence Studies

Nicotine transdermal delivery systems (nicotine-TDSs) have been evaluated clinically and found to provide effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a rate of permeation across the human cadaver skin comparable to the steady-state permeation rates attained by Habitrol™ and Nicoderm® systems. Clinical studies completed in two ethnic groups have demonstrated that this newly-developed nicotine-TDS is clinically effective and has yielded minimal skin irritation. As part of technical transfer program, a clinical study was initiated in 18 non-obese non-smoking Taiwanese, using Latin-square design, to compare the systemic bioavailability and pharmacokinetic profile of nicotine delivered transdermally from the nicotine-TDSs fabricated at technology licensee (Sintong nicotine-TDS) in comparison with that from the technology developer (TBS nicotine-TDS), using one marketed nicotine-TDS (Habitrol™ system) as the reference product. In vitro release and skin permeation studies of nicotine from the nicotine-TDSs manufactured at both licensor and licensee were found similar in kinetic profiles and comparable in rates. Since the patch size of these nicotine-TDSs studied was smaller than the marketed product used (10 cm² for both Sintong and TBS nicotine-TDSs, versus 20 cm² for Habitrol™ system), the daily doses of nicotine delivered to the volunteers are equivalent between Sintong and TBS nicotine-TDSs [9.58 (± 2.23) vs. 8.76 (± 1.88) mg/day/patch] but are lower than that from Habitrol™ system [15.13 (± 4.05) mg/day/patch]. Thus, for the statistical analysis of the pharmacokinetic parameters obtained need to be corrected for the difference in patch size and daily nicotine dose delivered. The results of statistical analysis suggested that Sintong and TBS nicotine-TDSs are bioequivalent to Habitrol™ system.     

Transdermal Nicotine Delivery Systems: Multi-institutional Cooperative Bioequivalence Studies

Abstract

Nicotine transdermal delivery systems (nicotine-TDSs) have been evaluated clinically and found to provide effective assistance to smokers in smoking cessation with minimal occurrence of withdrawal symptoms. However, substantial skin reactions have been reported with the four nicotine-TDSs marketed recently. To reduce the skin reactions, a new type of nicotine-TDS has been recently developed. In vitro skin permeation studies demonstrated that this nicotine-TDS yields a constant skin permeation profile with a rate of permeation across the human cadaver skin comparable to the steady-state permeation rates attained by Habitrol? and Nicoderm® systems. Clinical studies completed in two ethnic groups have demonstrated that this newly-developed nicotine-TDS is clinically effective and has yielded minimal skin irritation. As part of technical transfer program, a clinical study was initiated in 18 non-obese non-smoking Taiwanese, using Latin-square design, to compare the systemic bioavailability and pharmacokinetic profile of nicotine delivered transdermally from the nicotine-TDSs fabricated at technology licensee (Sintong nicotine-TDS) in comparison with that from the technology developer (TBS nicotine-TDS), using one marketed nicotine-TDS (Habitrol? system) as the reference product. In vitro release and skin permeation studies of nicotine from the nicotine-TDSs manufactured at both licensor and licensee were found similar in kinetic profiles and comparable in rates. Since the patch size of these nicotine-TDSs studied was smaller than the marketed product used (10 cm² for both Sintong and TBS nicotine-TDSs, versus 20 cm² for Habitrol? system), the daily doses of nicotine delivered to the volunteers are equivalent between Sintong and TBS nicotine-TDSs [9.58 (± 2.23) vs. 8.76 (± 1.88) mg/day/patch] but are lower than that from Habitrol? system [15.13 (± 4.05) mg/day/patch]. Thus, for the statistical analysis of the pharmacokinetic parameters obtained need to be corrected for the difference in patch size and daily nicotine dose delivered. The results of statistical analysis suggested that Sintong and TBS nicotine-TDSs are bioequivalent to Habitrol? system.     

Nicotine Skin Penetration Characteristics Using Aqueous & Non-Aqueous Vehicles,Anionic Polymers,and Siucone Matrices

Abstract

Nicotine is a rational candidate for transdermal delivery for smoking withdrawal. In vitro experiments were performed to characterize nicotine skin penetration and some factors affecting skin penetration. These included pH, nonaqueous solvents, and anionic polymers. Nicotine penetrated skin rapidly, and fairly high doses can be delivered transdermally. A 30% aqueous solution vehicle, as has been administered transdermally in clinical trials, produced very rapid initial absorption but the absorption rate decreased with time. Because nicotine has such high skin permeability, one objective in developing a delivery system would be to control the delivery rate, rather than allowing skin permeability to be rate-limiting. A feasible approach to a rate-controlled delivery system was to use vulcanized polydimethylsiloxane as a monolithic matrix.     

Kinetic Evaluation of Transdermal Nicotine Delivery Systems

The skin permeation and release kinetics of nicotine from four nicotine-releasing transdermal delivery systems (TDS) marketed recently was investigated under identical conditions to evaluate the effect of system design and the interchangeability of these products. In the study, hairless rat skin was first used as an animal model to evaluate the permeation mechanisms of various TDS's, which were then verified by studying the permeation through human cadaver skin. Three of the four TDS's were found to deliver nicotine at zero^th-order permeation kinetics at steady state with permeation rate ranging from 0.072 - 0.197 mg/cm²/hr, while the fourth one produced a triphasic zero^th-order permeation rate profile. Three TDS's released nicotine at non-linear manner, which could be described by a linear Q vs. t^1/2 relationship, while one TDS yielded a constant release at steady state. The different skin permeation profiles of nicotine delivered by these TDS's could be explained by the difference in their system designs and structural compositions.     

Kinetic Evaluation of Transdermal Nicotine Delivery Systems

Abstract

The skin permeation and release kinetics of nicotine from four nicotine-releasing transdermal delivery systems (TDS) marketed recently was investigated under identical conditions to evaluate the effect of system design and the interchangeability of these products. In the study, hairless rat skin was first used as an animal model to evaluate the permeation mechanisms of various TDS's, which were then verified by studying the permeation through human cadaver skin. Three of the four TDS's were found to deliver nicotine at zero^th-order permeation kinetics at steady state with permeation rate ranging from 0.072 - 0.197 mg/cm²/hr, while the fourth one produced a triphasic zero^th-order permeation rate profile. Three TDS's released nicotine at non-linear manner, which could be described by a linear Q vs. t^1/2 relationship, while one TDS yielded a constant release at steady state. The different skin permeation profiles of nicotine delivered by these TDS's could be explained by the difference in their system designs and structural compositions.     

Acrylic Matrix Type Nicotine Transdermal Patches: In Vitro Evaluations and Batch-to-Batch Uniformity

Abstract

Nicotine transdermal patches (NTPs) were fabricated using an acrylic pressure sensitive adhesive emulsion to form a transparent matrix film. An automated thin layer chromatography (TLC) plate scraper was used to control the thickness of the cast nicotine matrix film. The in vitro release behavior and permeation of nicotine across abdominal human epidermis (HE) from the NTPs was studied using United States Pharmacopeia (USP) dissolution apparatus 5 (paddle over disk) and modified Franz-diffusion cell, respectively. The release of nicotine from the NTPs showed a good linear correlation with the square root of time (R²>0.99). This indicated a matrix diffusion controlled-release mechanism. The surface morphology of the matrix of the NTP was uniform and nonporous before and after release, indicating that the dried adhesive nicotine matrix was a homogeneous single-phase film. Neither the nicotine content in the range 4.70–8.41% w/w nor the film thicknesses of the NTPs affected the apparent diffusion coefficient of nicotine in the acrylic matrix. A good relationship between the amount of nicotine permeated across the HE and the square root of time was also observed with R²>0.98. This study also showed that the NTPs provided a good delivery system with more than 65% of the nicotine delivery being controlled by the device. Moreover, the release of nicotine from six production batches met the criteria of USP 24. This finding presented a good potential of this method for upscaling to industrial manufacturing.     

Nicotine aerosol generation from thermally reversible zinc halide complexes using the Staccato system

Application of the Staccato system to liquid drugs presents unique technological challenges. Liquids, such as nicotine, do not form physically stable films on vaporization substrates. We identified two thermally reversible zinc halides (ZnCl2 and ZnBr2) that complex with nicotine in a 1:2 mol ratio (zinc halide: nicotine) that can be coated as a solid film. Feasibility studies indicated that the chloride complex liberates a higher fraction of nicotine upon heating whereas the nicotine aerosol purity for both complexes was approximately 99%. Using a multidose Staccato device previously used in a Phase I clinical trial, we demonstrated that highly pure nicotine aerosol can be reliably generated from the chloride complex with the following qualities: aerosol purity approximately 99%, single emitted dose approximately 117 microg, particle fraction approximately 57%, and mean particle size approximately 0.8 microm. These results were supported by thermogravimetric analysis and differential scanning calorimetry.     

Nicotine-like discriminative stimulus effects of acetylcholinesterase inhibitors and a muscarinic receptor agonist in Rhesus monkeys

Acetylcholinesterase (AChE) inhibitors and positive allosteric nicotinic acetylcholine receptor (nAChR) modulators are potential pharmacotherapies for nicotine dependence. Because some smoking cessation aids (e.g. varenicline) appear to work by mimicking the effects of nicotine, we used drug discrimination to examine whether AChE inhibitors and nAChR allosteric modulators mimic the effects of nicotine. Rhesus monkeys discriminated 1.78?mg/kg of nicotine s.c. under an FR5 schedule of stimulus-shock termination. Nicotine and the AChE inhibitors donepezil and galantamine dose-dependently increased responding on the nicotine-appropriate lever with ED₅₀ values of 0.35, 0.22, and 0.77?mg/kg, respectively. Donepezil (0.56?mg/kg) produced nicotine-like effects for at least 6?h, whereas the duration of action of galantamine (1.78?mg/kg) was less than 3?h. The positive allosteric nAChR modulator PNU-120596 (up to 10?mg/kg) and midazolam (up to 1.0?mg/kg) produced no more than 22% nicotine-lever responding. Oxotremorine, a muscarinic acetylcholine receptor agonist that was used to explore the extent to which muscarinic receptor agonism might contribute to the effects of AChE inhibitors, produced 94% nicotine-lever responding (ED₅₀ value 0.013?mg/kg). The muscarinic antagonist atropine significantly antagonized the effects of both oxotremorine and nicotine; however, the dose of atropine antagonizing oxotremorine was smaller than the dose required to antagonize nicotine. Collectively, these results suggest that AChE inhibitors can mimic the effects of nicotine by indirectly stimulating both nicotinic and muscarinic receptors. Inasmuch as some smoking cessation aids work by exerting nicotine-like effects, the current results are consistent with the potential use of AChE inhibitors as novel smoking cessation aids.     

Permeation Studies Comparing Cobra Skin with Human Skin Using Nicotine Transdermal Patches

Cobra skin (Naja Naja Khaotia) was used as a barrier for an in vitro permeation study using nicotine. Fluxes of nicotine that permeated from Nicotinell ® through cobra skin (CS) taken from the head, body, and tail were 233.93 ± 16.08, 206.87 ± 19.00, and 211.26 ± 22.93 μg/cm²/hr^1/2, respectively (n=6). This indicated no significant difference (p >. 05). Abdominal human epidermis (HE), obtained from cadavers, and the CS provided identical permeation kinetics for nicotine, which can be described by M_t = 4M_α=(Dt π L²)^1/2. The mean flux of nicotine formulated as an acrylic transdermal patch that permeated through HE was 137.92 ± 67.79 μg/cm²/hr^1/2 (4 specimens, n= 12), whereas that through CS was 180.13 ± 41.05 μg/cm²/hr^1/2 (4 specimens, n= 15). The ratio of the fluxes of nicotine from formulated patches having three different nicotine contents using CS and HE was 1.22 to 1, respectively, for each of the patches irrespective of nicotine content. The coefficients of variation of the nicotine permeated were 22.79% and 49.15% for CS and HE, respectively, that is, a narrower variation of results was obtained with CS. This indicated that CS could be used for nicotine permeation studies.     

In Vitro Study of Transdermal Nicotine Delivery: Influence of Rate-Controlling Membranes and Adhesives

The objective of this study was to evaluate the influence of a rate-controlling membrane and adhesive on the in vitro permeation of nicotine. The physicochemical properties of the adhesive, including adhesion and rheology (viscosity), were also detected. Higher permeability of nicotine was observed through a hydrophilic membrane than through a hydrophobic membrane. Natural rubber and silicone were used as the adhesive bases, respectively. The silicone adhesive showed the highest adhesion among all adhesive formulations. To increase the adhesion of natural rubber, a tackifier (polyisoprene) and a secondary tackifier (terpene polymer; Px 1150®) were incorporated into the formulations to achieve acceptable adhesion. The nicotine permeation through silicone adhesive and three natural rubber adhesives with the secondary tackifier (2%, 4%, and 6% Px 1150) was close to that from a commercially available patch (Habitrol®), although the loading amount of nicotine was not the same. A longer lag time during the in vitro permeation study of nicotine was required for the adhesives prepared in our laboratory than for the commercially available patch.     

In Vitro Study of Transdermal Nicotine Delivery: Influence of Rate-Controlling Membranes and Adhesives

The objective of this study was to evaluate the influence of a rate-controlling membrane and adhesive on the in vitro permeation of nicotine. The physicochemical properties of the adhesive, including adhesion and rheology (viscosity), were also detected. Higher permeability of nicotine was observed through a hydrophilic membrane than through a hydrophobic membrane. Natural rubber and silicone were used as the adhesive bases, respectively. The silicone adhesive showed the highest adhesion among all adhesive formulations. To increase the adhesion of natural rubber, a tackifier (polyisoprene) and a secondary tackifier (terpene polymer; Px 1150®) were incorporated into the formulations to achieve acceptable adhesion. The nicotine permeation through silicone adhesive and three natural rubber adhesives with the secondary tackifier (2%, 4%, and 6% Px 1150) was close to that from a commercially available patch (Habitrol®), although the loading amount of nicotine was not the same. A longer lag time during the in vitro permeation study of nicotine was required for the adhesives prepared in our laboratory than for the commercially available patch.     

Acrylic matrix type nicotine transdermal patches: in vitro evaluations and batch-to-batch uniformity

Nicotine transdermal patches (NTPs) were fabricated using an acrylic pressure sensitive adhesive emulsion to form a transparent matrix film. An automated thin layer chromatography (TLC) plate scraper was used to control the thickness of the cast nicotine matrix film. The in vitro release behavior and permeation of nicotine across abdominal human epidermis (HE) from the NTPs was studied using United States Pharmacopeia (USP) dissolution apparatus 5 (paddle over disk) and modified Franz-diffusion cell, respectively. The release of nicotine from the NTPs showed a good linear correlation with the square root of time (R2 > 0.99). This indicated a matrix diffusion controlled-release mechanism. The surface morphology of the matrix of the NTP was uniform and nonporous before and after release, indicating that the dried adhesive nicotine matrix was a homogeneous single-phase film. Neither the nicotine content in the range 4.70-8.41% w/w nor the film thicknesses of the NTPs affected the apparent diffusion coefficient of nicotine in the acrylic matrix. A good relationship between the amount of nicotine permeated across the HE and the square root of time was also observed with R2 > 0.98. This study also showed that the NTPs provided a good delivery system with more than 65% of the nicotine delivery being controlled by the device. Moreover, the release of nicotine from six production batches met the criteria of USP 24. This finding presented a good potential of this method for upscaling to industrial manufacturing.     

Rational Design of a Stable,Freeze-Dried Virus-Like Particle-Based Vaccine Formulation

Virus-like particles (VLPs) have been extensively explored as vaccine candidates since the mid-1980s. Numerous VLPs have been designed as vaccines for prevention of virus-induced infectious diseases and for the therapeutical treatment of chronic diseases and drug addiction. Recently, a vaccine against nicotine addiction, which is based on VLPs of the RNA phage Qb to which nicotine haptens are covalently coupled via succinimate linkers (NicQb), has attracted a great deal of interest. Phase II clinical trials with this vaccine have shown that it is efficacious for smoking cessation in humans when antinicotine antibody levels are sufficiently high. For commercialization, the development of stable formulations enabling storage for prolonged periods is required. Hereby, lyophilization, a well-established method leading to stable and dry formulations, is often applied. In this study, we investigated the influence of different pH values and various excipients such as surfactants, polyols, sugars, and salts on the stability of NicQb in liquid formulations, during freeze thawing, freeze drying, and finally upon storage of the dried product. Lyophilized NicQb formulations were developed which were stable over 6 months at ambient temperature with fully retained biological activity. Hereby, it was found that a combination of the surfactant polysorbate 20 and the disaccharide trehalose was capable to prevent NicQb aggregation and to preserve its integrity (nicotine binding and integrity of VLP shell). Furthermore, asymmetrical flow field-flow fractionation (AF4), a new, promising analytical tool, was established for the investigation of VLP stability.     

Development and Evaluation of Transdermal Salbutamol Delivering Systems

ABSTRACT

The transdermal drug delivery systems based on polymeric pseudolatex and matrix diffusion controlled systems for salbutamol were prepared and compared for in vitro skin permeation profile and in vivo performances. Poly (isobutylene) was used as release controlling polymer in both the systems. In vitro skin permeation was studied using the human cadavar skin in franz diffusion cell. Permeation rate constants for matrix diffusion controlled system and pseudolatices were 10.625 and 13.750 mcg/hr/cm² respectively. The prepared transdermal systems were tested on human volunteers having chronic reversible airways obstruction and compared with oral treatments (Asthaline). The in vivo drug plasma profiles following transdermal and oral treatments reveal that although peak plasma level by oral administration was higher in comparison with the transdermal treatments, troughs and peaks were discernible at dosing times. In the case of transdermal treatments, constant drug plasma and FEV₁ levels were recorded indicating controlled and systemic delivery of drug spaced over 30 hours. Among the prepared transdermal drug delivery systems, pseudolatices demonstrated better drug plasma profile, maintained at relatively higher level and flatter in appearance. The relative performance of the systems was noted to reflect in AUC and FEV₁.     

Analysis of nicotine and its oxidation products in nicotine chewing gum by a molecularly imprinted solid-phase extraction

Chromatographic stationary phases showing exceptional selectivity for nicotine can be prepared by the technique of molecular imprinting. Such phases were used in the search for a rapid cleanup step for nicotine and some of its oxidation products in chewing gum formulations. Thus, using an organic mobile phase, the nicotine analytes from chewing gums dissolved in nonpolar solvent were retained, whereas the nonpolar matrix eluted close to the void peak. A subsequent switch to an acidic mobile phase resulted in elution of the analytes as one sharp peak. Due to weak binding of the less basic oxidation products, other imprinted polymers were tested, and the solid-phase extraction procedure was optimized. Polymers were prepared using various functional and cross-linking monomers, templates, porogens and thermal treatments. This resulted in phases that, when compared with a nonimprinted or a C18 reversed-phase column, showed significantly higher recoveries of the analytes. Furthermore, no bleeding of template from the phases could be detected. The cleanup step was coupled off-line to reversed-phase HPLC, and the efficiency of the analysis was compared with and without the cleanup step. Three out of four analytes were quantitatively recovered using the imprinted phase, whereas, using the nonimprinted phase, only nicotine was recovered. Without the cleanup step, none of the analytes could be determined using the reversed-phase HPLC method.     

Influence of hydroxypropyl-beta-cyclodextrin on the transdermal permeation and skin accumulation of oxybenzone

The objective of the present study was to determine the effects of hydroxypropyl-β-cyclodextrin (HPCD) concentration on the transdermal permeation and skin accumulation of a model ultraviolet (UV) absorber, oxybenzone. The concentration of oxybenzone was held constant at 2.67 mg/mL for all formulations, while the HPCD concentrations varied from 0 to 20% (w/w). Complexation of oxybenzone by HPCD was demonstrated by differential scanning calorimetry. A modified Franz cell apparatus was used in the transdermal experiments, with aliquots of the receptor fluid assayed for oxybenzone by high-performance liquid chromatography. From the permeation data, flux of the drug was calculated. Skins were removed from the diffusion cells at specified time points over a 24-hr period and the oxybenzone content in the skin determined. The aqueous solubility of oxybenzone increased linearly with increasing HPCD concentration, following a Higuchi A_L-type complexation. The stability constant of the reaction was calculated from the phase-solubility diagram and found to be 2047 M^-1. As the concentration of HPCD was increased from 0 to 10%, transdermal permeation and skin accumulation of oxybenzone increased. Maximum flux occurred at 10% HPCD, where sufficient cyclodextrin was added to completely solubilize all oxybenzone. When the concentration of HPCD was increased to 20%, both transdermal permeation and skin accumulation decreased. These data suggest the formation of a drug reservoir on the surface of the skin.     

Influence of Hydroxypropyl- β-Cyclodextrin on the Transdermal Permeation and Skin Accumulation of Oxybenzone

ABSTRACT

The objective of the present study was to determine the effects of hydroxypropyl-β-cyclodextrin (HPCD) concentration on the transdermal permeation and skin accumulation of a model ultraviolet (UV) absorber, oxybenzone. The concentration of oxybenzone was held constant at 2.67 mg/mL for all formulations, while the HPCD concentrations varied from 0 to 20% (w/w). Complexation of oxybenzone by HPCD was demonstrated by differential scanning calorimetry. A modified Franz cell apparatus was used in the transdermal experiments, with aliquots of the receptor fluid assayed for oxybenzone by high-performance liquid chromatography. From the permeation data, flux of the drug was calculated. Skins were removed from the diffusion cells at specified time points over a 24-hr period and the oxybenzone content in the skin determined. The aqueous solubility of oxybenzone increased linearly with increasing HPCD concentration, following a Higuchi A_L-type complexation. The stability constant of the reaction was calculated from the phase-solubility diagram and found to be 2047 M^?1. As the concentration of HPCD was increased from 0 to 10%, transdermal permeation and skin accumulation of oxybenzone increased. Maximum flux occurred at 10% HPCD, where sufficient cyclodextrin was added to completely solubilize all oxybenzone. When the concentration of HPCD was increased to 20%, both transdermal permeation and skin accumulation decreased. These data suggest the formation of a drug reservoir on the surface of the skin.     

Evaluation of Polyvinyl Alcohol Hydrogel as Sustained-Release Vehicle for Transdermal Sytem of Bunitrolol-HCL

In order to evaluate a bunitrolol (β-blocker preparation using poly(vinyl alchol) (PVA) hydrogel for hypertension as a transdermal delivery system, in vitro release characteristics and the permeation of bunitrolol through rat sking from hydrogel and the bunitrolol plasma profile after application onto abdominal skin in rats were examined. The PVA hydrogel containing bunitrolol-HCl was prepared by a low temperature crystallization method. The release of bunitrolol from PVA hydrogel followed with Ficklan diffusion (Higuchi model); the drug relaase, profile versus square root of relase. The release rate and premeation through rat skins of bunitrolol from hydrogels affected with preparation at various physical and chemical states. Longer freezing times, higher polymerization and higher concentration of PVA resulted in lower permeation. These results had relations with the results of release tests. Higher pH of preparation resulted in a higher permeation of bunitrolol, which did not have a relaion with the results of release tests. The plasma concentration of bunitrolol after application of hydrogel preparation onto the abdominal skins were relatively high at early times and sustained a plateau level during 48 h in rates. In conclusion, transdermal delivery system using PVA hydrogel is favorable with prolonged action for low available drugs such as bunitrolol-HCl.     

Development and Evaluation of Transdermal Salbutamol Delivering Systems

Abstract

The transdermal drug delivery systems based on polymeric pseudolatex and matrix diffusion controlled systems for salbutamol were prepared and compared for in vitro skin permeation profile and in vivo performances. Poly (isobutylene) was used as release controlling polymer in both the systems. In vitro skin permeation was studied using the human cadavar skin in franz diffusion cell. Permeation rate constants for matrix diffusion controlled system and pseudolatices were 10.625 and 13.750 mcg/hr/cm² respectively. The prepared transdermal systems were tested on human volunteers having chronic reversible airways obstruction and compared with oral treatments (Asthaline). The in vivo drug plasma profiles following transdermal and oral treatments reveal that although peak plasma level by oral administration was higher in comparison with the transdermal treatments, troughs and peaks were discernible at dosing times. In the case of transdermal treatments, constant drug plasma and FEV₁ levels were recorded indicating controlled and systemic delivery of drug spaced over 30 hours. Among the prepared transdermal drug delivery systems, pseudolatices demonstrated better drug plasma profile, maintained at relatively higher level and flatter in appearance. The relative performance of the systems was noted to reflect in AUC and FEV₁.