A novel method for determination of the filling level in the feed frame of a rotary tablet press.

AIM: The aim of this study was to investigate whether the filling level within the feed frame of a rotary tablet press can be quantified by laser triangulation combined with the angle recognition of one paddle wheel via rotary encoder. SIGNIFICANCE: Rotary tablet press feed frames are supposed to assure a uniform die filling and, thus, to guarantee the weight and content uniformity of the resulting tablets. Therefore, a constant bulk availability and flow within the feed frame is crucial and has to be ensured by the feed frame design and the operating conditions. So far, there is no instrument available to monitor the bulk filling level or the bulk distribution within feed frames. METHODS: Calcium phosphate dihydrate was used as model powder. The powder surface level was determined via laser triangulation and the angle position of the paddle wheel was monitored via incremental rotary encoder. The data of both parameters was acquired synchronously and evaluated by in-house written software. RESULTS: Different powder masses led to significantly different filling level signals. The experiments showed a high reproducibility of the determined filling levels. Furthermore, an influence of the rotational speed on the powder distribution was observed. CONCLUSIONS: The developed instrument may be used for quantification of the volumetric filling level within rotary tablet press feed frames. It may either be used to better understand the powder behavior within feed frames or for improvement of the die filling process by implementing the device into a feedback loop.

Mixture design approach for early stage formulation development of a transdermal delivery system.

Transdermal delivery systems (TDS) consisting of mixtures of adhesives also named multiple polymer adhesive systems are rarely found in the market and research has only been performed on a few of them. Following the principles of ICH Q8, a Design of Experiments (DOE) approach was selected for the formulation development. For evaluation of the statistical method of "mixture design", blends of silicon adhesive, acrylic adhesive, oleyl alcohol as a surfactant and ibuprofen as a model drug were considered to be combined at different concentrations. A randomized design of 16 runs with five replicates and five runs to estimate the lack of fit (LOF) was generated. Samples were tested for adhesion properties, stability of the wet mixes, solubility of the API in the matrix and appearance of the matrix. After performing an ANOVA with the results, response surfaces of tack, shear adhesion, extent of creaming, crystallization behavior, droplet size and droplet size range were derived as contour plots. It could be shown that crystal growth of ibuprofen correlates well with droplet size and droplet size range, where lowest values for crystallization were found with mixtures containing small droplets. However, it was observed that oleyl alcohol showed no positive effect on the miscibility of the polymers and no improvement of the solubility of ibuprofen in the mixtures. With a reasonable number of experiments, the development of a design space for a TDS via mixture design gave valuable information on the product as well as on the interactions of the components.

Tableting properties of silica aerogel and other silicates.

CONTEXT: In solid oral dosage forms silicates are commonly used as glidants in low concentration. However, due to their large specific surface area, silicates may also be used as carrier materials for drugs. Moreover, silicates allow amorphisation of drugs by co-grinding or processing with supercritical fluids. OBJECTIVE: The aim of this study was to investigate the physical and the tableting properties of Silica Aerogel (special type of silica with an extremely large specific surface area), Neusilin(®) US2 (magnesium aluminometasilicate), Florite(®) (calcium silicate) and Aerosil(®) 200 (colloidal silica). MATERIALS AND METHODS: Powder blends of Avicel(®) PH102 (microcrystalline cellulose) and different amounts of the respective silicate were compacted and analyzed for their tabletability (tensile strength vs. compaction pressure) as well as their Heckel plot. RESULTS AND DISCUSSION: With Neusilin(®) the tabletability appeared to be independent of the silicate concentration, whereas with Florite(®) an increasing silicate concentration led to a higher tensile strength. In contrast, the addition of Silica Aerogel and Aerosil(®) resulted in a decrease of the tensile strength. With Aerosil(®) a maximum tolerable concentration of 20% [w/w] was determined. Plastic deformation of all powder blends decreased with increasing silicate concentration. This effect was most pronounced with Aerosil(®) and least with Florite(®). CONCLUSION: Tablets with acceptable tensile strength were obtained with all plain silicates except for Aerosil(®). Therefore, these silicates may be used in tablet formulations, e.g. as carrier materials for liquid or amorphous drugs.

Comparison of traditional and novel tableting excipients: physical and compaction properties.

CONTEXT: Novel tableting excipients are continuously developed and advertised with superior flow and compaction characteristics. OBJECTIVE: The objective of this study was to compare two traditionally used and two novel tableting excipients with regard to their physical and tableting properties as well as their magnesium stearate sensitivity. Avicel(®) PH102 (microcrystalline cellulose) was compared to the novel co-processed excipient Prosolv(®) SMCC90 (silicified microcrystalline cellulose), whereas Anhydrous Emcompress(®) (anhydrous dicalcium phosphate) was compared to the novel spherically granulated excipient Fujicalin(®) (anhydrous dicalcium phosphate). MATERIALS AND METHODS: True density, particle size, specific surface area (SSA), flowability, tabletability, and magnesium stearate sensitivity of the excipients was determined. RESULTS AND DISCUSSION: Due to the silification process (Prosolv(®)) and the unique manufacturing process (Fujicalin(®)), the novel excipients showed a comparably larger SSA. Hardest tablets by far could be obtained with Prosolv(®), followed by Avicel(®) and Fujicalin(®). Avicel(®) and Prosolv(®) were sensitive to magnesium stearate, whereas Fujicalin(®) and Emcompress(®) did not show lubricant sensitivity. This confirms the plastic deformation behavior of microcrystalline cellulose and the brittle fracture of anhydrous dicalcium phosphate. CONCLUSION: Compared to the traditional excipients the investigated novel tableting excipients were advantageous with regard to their SSA and their tableting properties.

Pharmacodynamics and dermatopharmacokinetics of betamethasone 17-valerate: assessment of topical bioavailability.

BACKGROUND: The bioavailability of most topically delivered drugs is difficult to quantify, but is generally believed to be very low. With the exception of the vasoconstrictor assay for corticosteroids, no methodology to quantify the rate and extent of drug delivery to the skin has been validated. Recent research has examined the dermatopharmacokinetic (DPK) technique, which is based on stratum corneum (SC) tape-stripping. OBJECTIVE: To compare the in vivo bioavailability of different topical formulations of betamethasone 17-valerate (BMV) using the vasoconstrictor assay and the DPK method. METHODS: BMV was formulated in different vehicles and the drug concentration was adjusted to either (i) equal thermodynamic activity, or (ii) a range of values up to that corresponding to 80% of maximum thermodynamic activity. Vasoconstriction, an accepted and widely used method to determine bioavailability and bioequivalence of topical steroids, was quantified with a chromameter over 24 h post-removal of the formulation. Drug uptake into the SC was assessed by tape-stripping. RESULTS: BMV at the same thermodynamic activity in different vehicles provoked similar skin blanching responses, while DPK profiles distinguished between the formulations. Further, skin blanching responses and drug uptake into the SC clearly depended upon the absolute BMV concentration applied. However, while the saturable nature of the pharmacodynamic response was clear, the tape-stripping method distinguished unequivocally between the different formulations and different concentrations. CONCLUSIONS: The DPK approach offers a reliable metric with which to quantify transfer of drug from the vehicle to the SC, and may be useful for topical bioavailability and bioequivalence determinations.

Effects of various vehicles on skin hydration in vivo.

The stratum corneum, the outermost layer of the skin, regulates the passive loss of water to the environment. Furthermore, it is well accepted that drug penetration is influenced by skin hydration, which may be manipulated by the application of moisturizing or oleaginous vehicles. Measurements of transepidermal water loss (TEWL), and of skin hydration using a corneometer, were used to assess the effect of different vehicles on stratum corneum barrier function in vivo in human volunteers. A microemulsion significantly increased skin hydration relative to a reference vehicle based on medium chain triglycerides; in contrast, Transcutol(R) lowered skin hydration. TEWL measurements confirmed these observations.

Influence of the feed frame design on the powder behavior and the residence time distribution.

The feed frame system is one of the key elements of a rotary tablet press. The powder in the funnel flows through the feed frame system, which ensures a uniform powder flow to the die disc. The objective of the present study was to investigate the effect of different feed frame designs of a production-scale rotary tablet press on the residence time distribution of two microcrystalline cellulose blends, one of them serving as a tracer blend and the other serving as a filling material. With these powder blends, the effect of a reduction of the filling volume of a three chamber feed frame on the powder residence time was investigated. It was shown, that the volume reduction of the three chamber feed frame equipped with three modified large hub wheels led to a decrease of the powder residence time as well as to low intermixing of the powder particles. Furthermore, the residence time distribution within the three chamber feed frame was compared to that within a single chamber cone-shaped feed frame. Both feed frame designs had a similar filling volume but different powder paths through the respective feed frame chambers. The results showed that the single chamber feed frame led to a narrower distribution of the powder residence time and a lower intermixing than the three chamber feed frame. An interesting output of the study was that the variation of the feed frame design had a more pronounced effect on the powder behavior than the variation of the filling volume.

The effect of different feed frame components on the powder behavior and the residence time distribution with regard to the continuous manufacturing of tablets.

The present study focused on the effect of different feed frame components on the residence time distribution of a three-chamber feed frame system (Fill-O-Matic). A production-scale rotary tablet press was used to simulate the industrial manufacture of tablets. The powder residence time distribution was used to characterize the powder behavior in the Fill-O-Matic. Therefore, two powder blends based on microcrystalline cellulose, one of them serving as a plain powder blend (MCC blend) and the other blend (tracer blend) spray colored with an indigo carmine solution by a fluid bed granulator, were used. With these powder blends, the effect of the reduction of the Fill-O-Matic volume with a perspex disc on the residence time distribution was compared with the standard configuration of the Fill-O-Matic. Furthermore, the filling wheel design with regard to the rod shape and different gap size configurations between the feed frame and the die disc were investigated. Interestingly, the reduction of the feed frame volume led to a remarkable decrease of the mean residence time and the mean centered variance. Moreover, the results of the filling wheel design showed that the rod shape of the filling wheels had a high influence on the intermixing of the powder particles in the filling chamber, whereas the corresponding tablet weights and their relative standard deviation were not affected. The gap size between the feed frame and the die disc had low influence on the residence time distribution but an effect on the tablet weights and their standard deviation.

Analysis of the powder behavior and the residence time distribution within a production scale rotary tablet press.

This study focuses on the behavior of powder particles in a rotary tablet press with special focus on the feed frame system. To obtain a better knowledge of the continuous manufacturing of tablets, the experimental setup was carried out with a production scale rotary tablet press. The behavior of the powder particles at different flow rates through the tablet press, residual moisture contents, particle sizes, and amounts of tracer was investigated. The residence time distribution was evaluated using the tracer indigo carmine, which was sprayed onto microcrystalline cellulose particle as solution with fluidized bed spray granulator to obtain a tracer blend. The residence time distribution was increased by increasing the amount of tracer blend, and a transition from a plain MCC blend to the tracer blend with regard to continuous manufacturing was shown. Furthermore, it was found that an increase in the flow rates of the powder particles through the tablet press led to a decrease of the residence time distribution (Et). The variation of the flow rate had no influence on the mechanically applied strain at high throughputs, which was confirmed by a constant number of paddle passes (Npp). At the lowest flow rate, the Npp appears to be higher than the constant Npp values at higher flow rates. The residual moisture content did not shown any significant influence on the residence time distribution. The examination of the effect of different tracer blend particle sizes led to an interesting result: It was shown that the particle size segregation only had a low influence on Et. However, a comparably higher influence of the particle size segregation on the particle distribution in the produced tablets was demonstrated. Large particles were deposited at the top of the tablet surface whereas small particles were deposited at their bottom.

Solid state interactions between the proton pump inhibitor omeprazole and various enteric coating polymers.

The influence of the acidic film formers Eudragit L 100, HPMCAS-HF, HP-55, and shellac on the stability of the acid-labile proton pump inhibitor omeprazole in solid drug-polymer blends at accelerated storage conditions (40 degrees C/75% RH) was determined by fourier transform infrared spectroscopy (FTIR), modulated temperature differential scanning calorimetry (MTDSC), and high performance liquid chromatography (HPLC). As expected, acidic polymers caused a degradation of omeprazole which was manifested by discolorations and increasing amounts of degradation products. However, MTDSC curves and FTIR spectra did not show additional peaks resulting from the omeprazole degradation products. These methods appeared to be not sensitive enough to separate analytically the drug and polymer signals from those of the decomposition products. With HPLC a sufficient quantification of the degradation products was possible. HP-55 caused the highest degree of omeprazole degradation, followed by shellac, HPMCAS-HF, and Eudragit L 100. No correlation with the microenvironmental pH values generated by the acidic polymers at the applied storage conditions was found. The melting process and the dissolution of acidic impurities were figured out as possible reasons for the more pronounced decomposition of the drug in presence of HP-55 and shellac.

Quantification of omeprazole degradation by enteric coating polymers: an UV-VIS spectroscopy study.

The aim of this study was to investigate the degradation of the acid-labile proton-pump-inhibitor omeprazole in organic polymer solutions and aqueous dispersions of enteric coating polymers by UV spectroscopy. Furthermore, data were compared with those obtained in a previous HPLC study. For comparative purposes the cationic Eudragit RS 100 and the monomeric acid acetic acid were included in this study. The discolorations of degraded omeprazole solutions were analysed by VIS spectroscopy. UV-VIS spectra were recorded after preparation of the solutions and after 180 min of storage. The change of absorption was calculated as the difference of the absorption values at 305 nm. Degradation of omeprazole depends on the amount of acidic groups in the polymer structure. This decomposition manifests itself in a shifting of the absorption maximum to lower wavelengths and a decrease of absorption intensity. UV-VIS spectroscopy was used to determine the extent of degradation induced by enteric polymers. A good correlation of these results with previous HPLC data was found when excluding UV absorbing polymers. Nevertheless, values obtained by UV-VIS spectroscopy were always lower than those obtained by HPLC. For evaluation of the discoloration of degraded omeprazole solutions, VIS spectroscopy is a simple and fast method.

Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.

The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs.

Percutaneous penetration of local anesthetic bases: pharmacodynamic measurements.

Local anesthetics do not penetrate readily through human skin if applied in their salt form; however, if applied in their base form various effects may be observed, such as a decrease in pricking pain and a change in burning, itch, and thermal sensations. These effects occur after skin penetration and may be attributed to the action of the anesthetics on nociceptors and thermoreceptors, i.e., on C and Adelta nerve fiber respectively. As there is little known about the time course of the pharmacodynamic response of cutaneously applied local anesthetic bases, this study was conducted to characterize various local anesthetics pharmacodynamically by measuring thermal thresholds over time with a thermal sensory analyzer. The results show that the investigated local anesthetics affect thermal thresholds to a different extent, with tetracaine and lidocaine being most efficient. From the response versus time profiles of all eight study subjects various response parameters were obtained: only the cold sensation parameters proved suitable for characterization of the local anesthetics, possibly because cold receptors are located in the epidermis and can easily be reached. Lag times of onset are short and the maximum anesthetic effect is reached within 2-3 h. Cold sensation parameters correlate linearly with the solubility of the local anesthetic bases in medium chain triglycerides and with the drug flux of 50% saturation, indicating that medium chain triglycerides may have similar properties with regard to the local anesthetics solubility as the stratum corneum lipids.

Eudragit E as coating material for the pH-controlled drug release in the topical treatment of inflammatory bowel disease (IBD).

During an attack of ulcerative colitis the colonic pH of normally 6.4-7.0 drops to values of 2.3-4.7. The objective of this study was to investigate an acid-soluble polymer (Eudragit E) as coating material for multiple units (mini tablets) with regard to its ability to allow drug release only under the acidic conditions of the inflamed colon. Mini tablets (diameter 3 mm) containing 20% (w/w) of the model drug dexamethasone with or without the mucoadhesive swelling agent carbomer 934 (neutralized) were coated in a small coating pan with different amounts of an organic solution of Eudragit E leading to coating thicknesses of 150-400 microm. Drug release from the Eudragit E-coated cores at pH 2.0-5.0 starts after 10-50 min due to the rapid dissolution of the Eudragit E film. At pH 6.8 lag times of drug release depend on the composition of the cores and the thickness of the coating film: In the case of the carbomer-containing cores drug release is induced by disruption of the coating film due to swelling of the cores and lag times (up to 20 h) increase overproportionately with increasing coating thickness. With no swelling agent in the cores drug release at pH 6.8 is delayed due to the low erosion/dissolution rate of Eudragit E. Lag times of drug release (up to 33 h) increase in a linear manner with increasing coating thickness. Thus, Eudragit E, protected against dissolution in the stomach by an enteric coating, is a suitable coating polymer for drug release in acidic regions such as the inflamed colon.

Enhancing effects of lipophilic vehicles on skin penetration of methyl nicotinate in vivo.

Vehicle effects may be caused by thermodynamic effects and by specific (penetration enhancing) effects. To investigate the effects of various lipophilic vehicles on drug penetration, an in vivo permeability study was conducted with methyl nicotinate as the model drug. The drug was dissolved in the respective vehicles at concentrations that provide equal drug escaping tendencies. Drug solutions were applied to the upper arms of volunteers with a glass chamber system. To avoid drug depletion effects, drug disappearance rates were measured under steady-state conditions by the difference method. Enhancement factors were calculated from the steady-state flux values (i.e., drug disappearance rates per area unit) and compared with results from non-steady-state experiments. Significant enhancing effects (p < 0.01) were observed with dibutyl adipate, caprylic/capric acid triglycerides containing 5% phospholipids, isopropyl myristate, and mineral oil. Caprylic/capric acid triglycerides, cetearyl isooctanoate, and the standard vehicle dimethicone 100 were without effect on drug penetration. The explanation for the observed enhancing effects may be an interaction of the lipophilic liquids with the lipid bilayers of the stratum corneum that leads to a decrease of the barrier resistance.

Do local anesthetics have an influence on the percutaneous penetration of a model corticosteroid? An in vivo study using the vasoconstrictor assay.

Local anesthetics may exert nonspecific interactions with membrane components which can affect drug permeability. To investigate pharmacodynamically whether these membrane interactions lead to penetration enhancement of the coadministered model drug betamethasone-17-benzoate through human skin, the vasoconstrictor assay was used. Information on the penetration-enhancing properties of local anesthetic-containing vehicles compared to a plain standard were obtained from activity-response curves, where the enhancement factor was determined from the horizontal distance between the standard and a test in the linear range of the curves. The local anesthetics are able to enhance drug penetration through human skin to a different extent with lidocaine being the most efficient enhancer. An increase in the drug solubility and the diffusion coefficient in the stratum corneum due to membrane fluidization are possible mechanisms of action.

The maximum pharmacodynamic effect as a response parameter: pharmacokinetic considerations.

In previous human in-vivo studies measuring the maximum pharmacodynamic response to characterize cutaneously applied ointment preparations, it was observed that differences between various formulations caused by penetration enhancement led to different enhancement factors depending on the method used for determination of these factors from activity-response curves. To clarify this discrepancy, pharmacokinetic simulations have been performed based on an open one-compartment model with either first- or zero-order drug penetration kinetics and first-order elimination kinetics. Under the assumption that the maximum pharmacodynamic response corresponds to the maximum effective drug concentration in the receptor compartment, which represents the difference between the maximum drug concentration and the threshold concentration, drug concentration vs time profiles and dose-response curves were simulated. In addition, maximum effective concentrations were calculated and plotted against the logarithm of the thermodynamic drug activity to obtain activity-response curves. Relative bioavailability and enhancement factors were determined either from the horizontal distance between the curves of a standard and a test preparation, or as the ratio of the maximum effective concentration of test and standard formulations. A significant difference between the first-order and the zero-order input kinetics with regard to the evaluation of bioavailability and drug penetration enhancement was shown. Under finite dose conditions, i.e. first-order input kinetics from solution-type preparations, a misestimation of the factors usually occurs. Only under infinite dose conditions, i.e. if large preparation volumes are applied to achieve zero-order input kinetics, is the determination of bioavailability and enhancement factors from dose- and activity-response curves accurate.

An attempt to clarify the mechanism of the penetration enhancing effects of lipophilic vehicles with differential scanning calorimetry (DSC).

In a previous in-vivo skin penetration study, it was observed that certain lipophilic liquid vehicles enhanced drug penetration, whilst others did not. To clarify the mechanism of skin penetration enhancement, isolated sheets of human stratum corneum were measured by differential scanning calorimetry (DSC), either untreated or after pretreatment with various lipophilic liquids (highly purified light mineral oil, isopropyl myristate, caprylic/capric acid triglycerides containing 5% phospholipids, dibutyl adipate, dimethicone 100, cetearyl iso-octanoate, caprylic/capric acid triglycerides), commonly used in ointment bases. All samples were analysed over a heating range of at least--10-130 degrees C. All DSC curves were evaluated with regard to the phase-transition enthalpies (peak areas) and peak maximum temperatures of the lipid-phase transitions at ca 75 and 85 degrees C. With the exception of dimethicone 100, cetearyl iso-octanoate and caprylic/capric acid triglycerides, all vehicles showed characteristic alterations of the phase-transition temperatures and enthalpies of the stratum corneum lipids. Mineral oil and isopropyl myristate caused a reduction of the enthalpy and a decrease of the phase-transition temperatures. These two vehicles are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly partially dissolve the lipids. Dibutyl adipate and caprylic/capric acid triglycerides containing 5% phospholipids decreased the phase-transition enthalpy only, probably due to dissolution or extraction of the stratum corneum lipids. These DSC results provide an explanation for the in-vivo penetration-enhancing effects observed previously.

The effect of cream and ointment bases on the steady state penetration of permeants through intact skin: the reciprocal of the onset time of a pharmacodynamic effect as parameter of response.

To characterize cream or ointment bases for cosmetic or pharmaceutical purposes with regard to their effect on permeant penetration through intact healthy skin, the measurement of the pharmacodynamic response of a suitable model drug incorporated in these bases has been shown to be a promising approach. In general, it may be distinguished between thermodynamic vehicle effects owing to different permeant escaping tendencies from the vehicles and penetration-enhancing vehicle effects resulting from a change of the stratum corneum structure, which manifests itself in an increase of the permeant diffusion coefficient and/or its solubility in this barrier. As the latency time of onset of a pharmacodynamic effect, usually used as reciprocal value, represents a suitable response parameter under certain circumstances, this study was done to further evaluate this parameter with regard to the determination of relative bioavailability and penetration enhancement data obtained from simulated dose- and activity-response curves assuming infinite dose conditions, i.e. zero order penetration kinetics and considering varying lag times of drug penetration. The results indicate that bioavailability and enhancement factors may be determined accurately from the horizontal distance between dose- or activity-response curves of a standard and a test preparation as long as the curves are parallel to each other, as it is the case with uniform lag times of permeant penetration. Non-parallel curves observed with varying lag times indicate an influence of the vehicles on the permeant diffusion coefficient in the barrier. Enhancement factors from these curves may be obtained after determination of the lag times from the plateau region of the curves, subsequent subtraction of these values from the measured latency time data, and finally plotting of the reciprocal data as a function of the drug activity. Enhancement factors then correspond to the inverse logarithm of the horizontal distances between the resulting parallel curves.

Effect of cutaneously applied nonionic surfactants and local anesthetic bases on thermal sensations.

With cutaneously applied local anesthetic bases various effects may be observed, such as a decrease in pricking pain and a change in burning, itch, and thermal sensations. These effects occur after skin penetration and may be attributed to the action of the anesthetics on nociceptors and thermoreceptors, i.e., on C and A delta nerve fibers, respectively. As little is known about the pharmacodynamic response of nonionic surfactants with a potentially anesthetic action such as polidocanol, this study characterizes nonionic surfactants pharmacodynamically by measuring thermal thresholds with a thermal sensory analyzer after cutaneous application. The results obtained with the nonionic surfactants were compared with data resulting from the cutaneous application of local anesthetic bases such as mepivacaine, bupivacaine, prilocaine, lidocaine, the 1:1 mixture of lidocaine and prilocaine contained in EMLA and a triple mixture consisting of lidocaine, prilocaine and tetracaine (1:1:1). The results show that none of the investigated surfactants affect thermal thresholds probably due to their high molecular weight. The same was observed with the anesthetics mepivacaine and bupivacaine. In contrast, prilocaine, lidocaine, the 1:1 mixture of lidocaine and prilocaine and the triple mixture consisting of lidocaine, prilocaine and tetracaine (1:1:1) proved to be potent local anesthetics. However, their pharmacodynamic responses do not differ significantly from each other.