Selective Laser Sintering of a Photosensitive Drug: Impact of Processing and Formulation Parameters on Degradation, Solid State, and Quality of 3D-Printed Dosage Forms.

This research study utilized a light-sensitive drug, nifedipine (NFD), to understand the impact of processing parameters and formulation composition on drug degradation, crystallinity, and quality attributes (dimensions, hardness, disintegration time) of selective laser sintering (SLS)-based three-dimensional (3D)-printed dosage forms. Visible lasers with a wavelength around 455 nm are one of the laser sources used for selective laser sintering (SLS) processes, and some drugs such as nifedipine tend to absorb radiation at varying intensities around this wavelength. This phenomenon may lead to chemical degradation and solid-state transformation, which was assessed for nifedipine in formulations with varying amounts of vinyl pyrrolidone-vinyl acetate copolymer (Kollidon VA 64) and potassium aluminum silicate-based pearlescent pigment (Candurin) processed under different SLS conditions in the presented work. After preliminary screening, Candurin, surface temperature (ST), and laser speed (LS) were identified as the significant independent variables. Further, using the identified independent variables, a 17-run, randomized, Box-Behnken design was developed to understand the correlation trends and quantify the impact on degradation (%), crystallinity, and quality attributes (dimensions, hardness, disintegration time) employing qualitative and quantitative analytical tools. The design of experiments (DoEs) and statistical analysis observed that LS and Candurin (wt %) had a strong negative correlation on drug degradation, hardness, and weight, whereas ST had a strong positive correlation with drug degradation, amorphous conversion, and hardness of the 3D-printed dosage form. From this study, it can be concluded that formulation and processing parameters have a critical impact on stability and performance; hence, these parameters should be evaluated and optimized before exposing light-sensitive drugs to the SLS processes.

Photostability of barnidipine in combined cyclodextrin-in-liposome matrices.

BACKGROUND: The improvement of barnidipine photostability was investigated in cyclodextrin or liposome matrices and in appropriate combinations of these matrices. These supramolecular systems allowed the preparation of liquid formulations, as an alternative to the current solid commercial specialties. MATERIALS & METHODS: Photodegradation stressing tests were performed according to the ICH rules and monitored by derivative spectrophotometry. Optimization was evaluated in terms of drug-inclusion efficiency. RESULTS: The photodegradation rate of barnidipine in ethanol proved rapid (residual percentage of 29.81%) after a radiation exposure of 225 kJ/m(2). The residual concentrations detected for liposome and cyclodextrin complexes were 42.90 and 72.03%, respectively. The best results were obtained when the drug-cyclodextrin complex was in turn entrapped in liposomes (residual percentage of 90.78%). CONCLUSION: The stability of the drug-in-cyclodextrin-in-liposome system increased significantly with a value close to that of solid formulations whose residual percentage was 96.03%.

Modelling nifedipine photodegradation, photostability and actinometric properties.

BACKGROUND: The photodegradation of drugs obeying unimolecular mechanisms such as that of nifedipine (NIF) were usually characterised in the literature by zero-, first- and second-order kinetics. This approach has been met with varying success. This paper addresses this issue and proposes a novel approach for unimolecular photodegradation kinetics. The photodegradation of the cardiovascular drug nifedipine is investigated within this framework. METHODS: Experimental kinetic data of nifedipine photodegradation were obtained by continuous monochromatic irradiation and DAD analysis. Fourth-order Runge-Kutta calculated kinetic data served for the validation of the new semi-empirical integrated rate-law model proposed in this study. RESULTS: A new model equation has been developed and proposed which faithfully describes the kinetic behaviour of NIF in solution for non-isosbestic irradiations at wavelengths where both NIF and its photoproduct absorb. NIF absolute quantum yield values were determined and found to increase with irradiation wavelength according to a defined sigmoid relationship. The effects of increasing NIF or excipients' concentrations on NIF kinetics were successfully modelled and found to improve NIF photostability. The potential of NIF for actinometry has been explored and evaluated. A new reaction order (the so-called Φ-order) has been identified and specifically proposed for unimolecular photodegradation reactions. CONCLUSION: The semi-empirical and integrated rate-law models facilitated reliable kinetic studies of NIF photodegradation as an example of AB(1Φ) unimolecular reactions. It allowed filling a gap in kinetic studies of drugs since, thus far, thermal first-order or a combination of first- and zero- order kinetic equations were generally applied for drug photoreactions in the literature. Also, a new reaction order, the "Φ-order", has been evidenced and proposed as a specific alternative for photodegradation kinetics.

Effect of laser irradiation on the stability of a photo-sensitive active pharmaceutical ingredient by Raman microscopy.

This study was conducted to investigate the effect of laser beam irradiation from a novel non-confocal laser Raman microscope on the stability of a photo-sensitive drug. The non-confocal Raman microscopy, which irradiates a low-power unfocused laser beam on the surface of the samples by controlling of optical system, was applied to characterize the stability of nifedipine as a photo-sensitive drug model. The time-dependent changes in the Raman spectra of nifedipine were monitored in order to evaluate the degradation of nifedipine during laser irradiation. The results were compared with the Raman spectra measured by using the confocal laser Raman microscopy which irradiates a low-power focused laser beam. The intensity of some peaks in the confocal Raman spectra significantly decreased depending on the irradiation-time length, compared to the non-confocal Raman macroscopic analysis. The photodegradation of nifedipine caused by the laser irradiation followed the first-order kinetics. The degradation rate constants of nifedipine with the non-confocal analysis were lower than those of nifedipine with the confocal analysis. Thus, the novel non-confocal laser Raman microscopy can be applied to reduce the degradation of the photo-sensitive drug during laser irradiation, and the results suggest that the non-confocal laser Raman microscopy will be a useful technique for the measuring of Raman spectra of photo-sensitive materials with a long-term exposure.

LED-array photocalorimetry: instrument design and application to photostability of nifedipine.

A photocalorimeter was designed to analyse quantitatively the photostability of pharmaceuticals. Its application is demonstrated with reference to two solution phase test systems; the photodegradations of 2-nitrobenzaldehyde (2-NB) and nifedipine. Light emitting diode (LED) arrays were used to illuminate the sample and reference channels of the calorimeter. Five LEDs were used to create an array from 360 to 700nm. A power supply system was constructed that zeroed the instrument by supplying a preset voltage to the sample side LEDs and varying that supplied to the reference LEDs until a zero calorimetric signal was obtained. The photodegradation of 2-NB was zero-order and varied in proportion to the input voltage supplied to the LED array. Analysis of the data (the rate of reaction was determined to be equal 1.04x10(-6)moldm(-3)s(-1) by pH titration) determined a reaction enthalpy of 5.0+/-0.6kJmol(-1). In the case of nifedipine, the LEDs in the array were operated individually in order to determine the causative wavelength of degradation. This was found to be 360nm, in agreement with the literature.

Photophysics and photochemical studies of 1,4-dihydropyridine derivatives.

The absorption and fluorescence properties of nifedipine (NPDHP), felodipine (CPDHP) and a series of structurally related 1,4-dihydropyridines were studied in aqueous solution and organic solvents of different properties. The absorption and fluorescence spectra were found to depend on the chemical nature of the substituents at the position 4 of the 1,4-dihydropyridine ring (DHP) and on solvent properties. In aqueous solution, the fluorescence spectra of 4-phenyl substituted compounds are blue-shifted with respect to the alkyl substituted compounds. The more fluorescent compound is CPDHP. Nifedipine is not fluorescent. All compounds, with the exception of CPDHP, present monoexponential fluorescence decay with very short lifetime (0.2-0.4 ns). CPDHP showed a biexponential emission decay with a long-lived component of 1.7 ns; this behavior is explained in terms of different conformers because of the hindered rotation of the phenyl group by the ortho-substitution. Analysis of the solvent effect on the maximum of the absorption spectrum by using the linear solvent-energy relation solvato-chromic equation indicates the redshifts are influenced by the polarizability, hydrogen bonding ability and the hydrogen bond acceptance of the solvent. Whereas, the fluorescence characteristics (spectra, quantum yields and lifetimes) are sensitive to the polarizabilty and hydrogen bond ability of the solvents. Photo-decomposition of nifedipine is dependent on the solvent properties. Faster decomposition rates were obtained in nonprotic solvents. The 4-carboxylic derivative goes to decarboxylation. Under similar conditions, the other DHP compounds did not show appreciable photodecomposition.

Photostability studies for micellar liquid chromatographic determination of nifedipine in serum and urine samples.

Nifedipine is a photosensitive compound that is converted into its 4-(2-nitrophenyl) pyridine and 4-(2-nitrosophenyl) pyridine homologue. In order to obtain the most adequate conditions for handling nifedipine solutions in the analytical laboratory, a number of studies on the decomposition of this compound were performed. A simple micellar liquid chromatographic procedure was described to determine nifedipine in different biological matrices such as serum and urine, and to control its decomposition. To perform the analysis, nifedipine was dissolved in 0.1 m SDS at pH 3 and chromatographed using a mobile phase containing 0.125 m SDS-3% pentanol, pH 3 on a C18 column and UV detection at 235 nm. The chromatographic analysis time was 8 min. The response of the drug for both biological matrices was linear in the 1-100 microg/mL range, with r2>0.997 at all times. Repeatability, intermediate precision (CV, %) and limits of quantification and detection (ng/mL) were 0.19, 4.3, 104 and 31 in serum and 0.81, 2.1, 136 and 41 in urine. The method developed here does not show interferences or matrix effects produced by endogenous compounds. Micellar media and mobile phases have the advantage of stabilising the compounds, thus preventing photodegradation and allowing the direct injection of biological samples.

Particular features of photolabile substances in tablets.

Nifedipine and molsidomine tablets are extremely photolabile drug preparations, even at cool room light. Compared to solutions the light spectrum responsible for photodegradation is moved towards the long-wavelength range corresponding to the bathochromic shift of light absorption in the solid state. In the case of nifedipine tablets light up to 500 nm, especially the range between 400-420 nm, is degrading. Molsidomine tablets are affected only by ultraviolet light, but not by visible light. In both cases light penetrates less than 1 mm into the tablets. For nifedipine tablets the exact penetration depth could be determined due to the discolouration of the drug substance upon irradiation. It varied from 360 microm to 880 microm depending on the drug content. Since the decomposition products of nifedipine act as photostabilizers by spectral overlay, light penetration and photodegradation in nifedipine tablets are limited. The formation of gaseous and liquid decomposition products in molsidomine tablets enhances photodegradation. Changes of the tablet structure as well as dissolution and migration processes are discussed. Furthermore the degradation products donot photostabilize the drug substance due to the missing light absorption above 300 nm.

A study of the photo-degradation kinetics of nifedipine by multivariate curve resolution analysis.

A multivariate curve resolution method based on the combination of Kubista approach and iterative target transformation method of Gemperline has been proposed. This method is a soft model and need no information about the spectrum of the product and mechanism of the reaction. The method was used to study the degradation kinetics of nifedipin, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxilic acid dimethyl ester, upon exposure to the light of a 40 W tungsten lamp. The spectra of the nifedipine, collected at different lighting times, were subjected to the factor analysis and two chemical components were detected in the reaction system. Pure spectra of the components involved and their concentration profiles were obtained. The results revealed that the photodecomposition kinetics of nifedipine is zero-order at the beginning of the reaction. However, when the reaction preceded more than 50%, the kinetics of reaction changed to a first-order manner. The rate constants for the zero-order and first order regions were estimated as regions (4.96+/-0.13) x 10(-9) M(-1) s(-1) and (6.22+/-0.10) x 10(-5) s(-1), respectively.

Photostability of extended-release matrix formulations.

The photostability of drugs has been widely studied while less attention is devoted to the possible modifications that UV light may induce on the excipients of a dosage form, in particular, on the functional polymers used to modulate drug delivery. In this work we have evaluated the effect of UV light on the release characteristics of extended-release matrix tablets containing hydroxypropylmethylcellulose (HPMC) or polyethylene oxide (PEO) as retarding polymers. Two different model drugs have been used: nifedipine (insoluble and photolabile drug) and diltiazem (soluble and photostable drug). Photodecomposition of nifedipine was evaluated and the formation of the photoproducts was followed during the dissolution process. Regarding the dissolution stability, the matrix tablets containing HPMC exposed to UV light have not shown significant differences in drug release profiles compared to the same non-irradiated formulation, while the matrix tablets containing PEO and exposed to the same conditions of UV light have shown a remarkable increase of drug release rate within the first minutes of the dissolution test (burst effect) which is particularly critical because it can cause the loss of the desired therapeutic control.

ICH guideline for photostability testing: aspects and directions for use.

The ICH guideline Q1B for photostability testing gives guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products. The choice of the irradiation method, although complying with the guideline demands, may effect test results. High irradiances may shorten testing times, but can lead to enforcement of photodegradation, which was demonstrated for molsidomine tablets. The exposure to an artificial light source (xenon lamp) was compared and correlated to natural daylight. Suitable testing methods for nifedipine and molsidomine tablets were developed. Deviating from the guideline recommendations, the presentation of powder samples should be done in tiny aluminium pans, facilitating the test procedure, minimising the risk of falsified test results due to improper sampling and improving reproducibility. When using glass dishes for the presentation of tablets to photostability testing, they should be lined by e. g. aluminium foil to avoid influences of light reflected from the sample tray.

The influence of formulation and manufacturing process on the photostability of tablets.

The formulation and the manufacturing process can significantly influence the photostability of tablets. Investigations of various formulation and manufacturing parameters were done with tablets containing nifedipine and molsidomine as highly light sensitive drugs. The effect of relevant formulation factors are stated. Whereas the particle size of the drug substance and the choice of the lubricant had no effect, the drug content, the compression diluent and geometric alterations significantly affected the photoinstability. Depending on the formulation drug losses varied between 30 and 55% after 12 h irradiation in a light testing cabinet (Suntest CPS+). Manufacturing parameters like compression force and direct compression versus granulation showed less serious influences. Nevertheless, photostability changes up to 10% were registered.

Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state.

Nifedipine is a highly photosensitive drug that requires restricted protection from light during manufacturing, storage and handling of its dosage forms. Inclusion complexation of nifedipine with cyclodextrins (CDs) could be advantageous in protecting the drug against the effect of light. In this study, solid inclusion complexes of nifedipine with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) were prepared using the coprecipitation method. The obtained solid inclusion complexes have been confirmed by differential scanning calorimetry (DSC), X-ray diffraction and infrared spectroscopy (IR). The IR spectra indicated partial inclusion of nifedipine molecules into CD cavities through the dihydropyridine ring. Inclusion complexation was also associated with a dramatic enhancement of drug dissolution with magnitudes depended on the type of CD. The effect of exposure to fluorescent lamp and sunlight on the photodegradation of uncomplexed and complexed nifedipine was tested. Photodegradation of nifedipine was monitored using a high performance liquid chromatographic (HPLC) assay method. Inclusion complexation of nifedipine showed to retard drug photodegradation as indicated by degradation rate constant lowering with values depended on light source and type of complexing agent. This effect was the least with beta-CD compared with that of modified beta-CD. It was also interesting to notice that inclusion complexation of nifedipine offered much higher protection against the effect of fluorescent lamp than that of sunlight. The obtained results suggests that the design of solid dosage forms of nifedipine such as a fast dissolving nifedipine tablets is possible with the advantages of low required light protection.

Photodegraded nifedipine stimulates uptake and retention of iron in human epidermal keratinocytes.

Photodegraded nifedipine has been shown to increase uptake of nontransferrin bound iron into erythroid cells. If iron could be loaded into keratinocytes, it might be possible to exploit epidermal desquamation for the purpose of eliminating potentially toxic amounts of iron from the body. We investigated the ability of photodegraded nifedipine to stimulate iron transport and accumulation in human epidermal keratinocytes. Nifedipine was degraded to its nitroso derivative by exposure to sunlight. 59Fe uptake was measured in keratinocyte monolayers, and total iron content was measured in stratified epidermal cultures. Photodegraded nifedipine increased iron uptake into keratinocytes 80-fold compared to controls. The effect of photodegraded nifedipine on iron uptake was rapid, was concentration dependent and occurred at physiologically relevant concentrations of nonprotein-bound iron. Stimulation of iron uptake by photodegraded nifedipine was independent of transferrin and worked equally well in the presence or absence of serum proteins. Iron content in keratinocytes was increased 3-fold by four daily treatments with photodegraded nifedipine. The increased iron content resulting from photodegraded nifedipine treatment was retained during a 4 d washout period. Photodegraded nifedipine may be a way delivering clinically significant amounts of iron to the epidermis.

Spectroscopic and HPLC studies of photodegradation of nilvadipine.

Photochemical decomposition of nilvadipine (NV), a derivative of 1,4-dihydropyridine (DHP), was studied. Photodegradation was carried out in the conditions recommended in the first version of the document issued by the International Conference on Harmonization (ICH), currently in force in the studies of photochemical stability of drugs and therapeutic substances. Methanol solutions of NV were irradiated with a high-pressure mercury arc lamp, type HBO 200 (300-400 nm). The maximum absorption of radiation at 365 nm was achieved by applying the interference filter and Wood's filter. The assessment of NV photodegradation was made on the basis of the UV spectrophotometric and high-performance liquid chromatographic (HPLC) methods. Quantitatively, the process was described with the calculated rate constants of decomposition k, time of decomposition of 50% of the compound to 5, and time of decomposition of 10% of the compound t(0.1). The two methods applied allowed a determination of the kinetic parameters of NV photodegradation from the relationship ln c = f(t). Using the Reinecke salt as a chemical actinometer, apparent quantum yields of photodegradation were obtained; after extrapolation to the time of irradiation zero, these gave the actual quantum yield (phi = 7.3 10(-5)). The quantum yield of fluorescence at lambda(exc) = 375 nm was about 9.3 x 10(-4) The methods used for evaluation of NV photodegradation were subjected to validation, and results of the analytical methods were statistically assessed by Snedecor F and Student t tests. The former test revealed no statistically significant difference between the variances obtained by the HPLC and UV spectrophotometric methods. Also, verification of the zero hypothesis of the Student t test on equality of means of the results obtained gave no significant diferences between the two methods.

The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipine.

The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I-III) participated in this ethically approved, randomised, cross-over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17-36 min. Plasma nifedipine levels were measured using a standard reverse-phase high-performance liquid chromatography method. The area under the plasma concentration-time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng x ml(-1) x h(-1)) was significantly higher than during the non-irradiation control session (median 174.5 ng x ml(-1) x h(-1)) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng x ml(-1) x h(-1)). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t 1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow.

Free radicals in irradiated drugs: an EPR study.

Exposure of dry powder forms of the drugs nitrendipine, nifedipine, felodipine, and nimodipine to gamma-radiation results in the formation of free radicals detected by electron paramagnetic resonance (EPR) spectroscopy. The four structurally related drugs show qualitatively identical EPR spectral features in terms of g-values, the qualitative descriptive parameter. These radicals are very stable, surviving long periods of time in excess of 9 months and possibly beyond conventional shelf-life of the drugs. The residual radical population is high enough to be detectable after long storage. Administration of such radiation-treated drugs may present patients with quantities of free radicals and possibilities of secondary cell damage.

Kinetics of contraction in depolarized smooth muscle from guinea-pig taenia coli after photodestruction of nifedipine.

1. The time course and kinetics of force development following activation by opening of L-type Ca2+ channels was investigated using photodestruction of the Ca2+ channel blocker nifedipine in smooth muscle from the guinea-pig taenia coli. 2. In muscles activated using high K+ and Ca2+ and subsequently inhibited with nifedipine, photodestruction of the drug using a strong ultraviolet light flash initiated a rapid contraction. The force initiated by photodestruction of nifedipine reached near-maximal levels. This procedure eliminates diffusional delays and can thus be used to investigate the kinetics of depolarization-induced contractions. 3. The rate of force development of contractions initiated by photodestruction of nifedipine was slower than that observed in maximally thiophosphorylated skinned fibres. This suggests the rate of force development is limited by activation steps in the activation cascade prior to the force generation of the cross-bridge system. 4. The rate of force development and the plateau force were dependent on the extracellular [CaCl2] suggesting that the intracellular [Ca2+] determines the rate of phosphorylation and force development. The delay between illumination and increase in force was about 300 ms. The delay was similar at low and high extracellular [CaCl2] indicating that buffering by superficial sarcoplasmatic reticulum does not introduce a delay in force development following activation of Ca2+ channels in this muscle.

Real time detection of photoreactivity in pharmaceutical solids and solutions with isothermal microcalorimetry.

PURPOSE: In this study an irradiation cell made as an accessory for an isothermal microcalorimeter is introduced, and its suitability for detection photoreactivity in pharmaceutical solutions and solids is demonstrated. The pharmaceuticals employed are chosen as sample materials to evaluate the usefulness and stability of the irradiation cell. METHODS: An irradiation cell has been constructed and tested in an isothermal microcalorimeter with pharmaceutical solutions and solids known to be sensitive to daylight or UV light. Light is produced with an Xe-arc lamp, split into two parts and introduced into calorimetric vessels with optical light cables. One of the vessels containing the reference sample gives the response to the heat absorbed by the material (radiant power), and the other vessel containing the sample material gives the response also to the photoreaction. The two irradiation cells are positioned in the sample sides of two separate twin microcalorimetric units. RESULTS: Nifedipine and L-ascorbic acid were found to be photosensitive in solutions and solid states, the extent of the degradation depending on the irradiation intensity and wavelength. The threshold values of the wavelength for the photoreactions, as well as the wavelengths for the maximum reaction rates, were estimated via the scanning irradiation measurements. The ability of photons with different energies to produce heat in the photosensitive reaction of nifedipine was calculated using constant lambda measurements. CONCLUSIONS: The technique introduced offers a rapid and versatile method to study the photosensitivity of materials in any state. In the measurements, various conditions can be simulated and thus provide information on the real behavior of materials.

Photodegraded nifedipine promotes transferrin-independent gallium uptake by cultured tumor cells.

UNLABELLED: It was reported previously that normal soft tissues accumulate 67Ga by a transferrin-dependent route, but uptake by tumors can be transferrin independent. It was also reported that, although overexpression of the transferrin receptor can promote Ga avidity, the transferrin-independent uptake of 67Ga is significant and can be augmented to exceed transferrin-mediated levels by increasing extracellular calcium. In assessing the effect of calcium channel blockers on uptake of 67Ga, it was observed that, after exposure to light (either visible or ultraviolet [UV]), nifedipine strongly potentiates the cellular uptake of 67Ga by a transferrin-independent process. METHODS: The effect of nifedipine on 67Ga uptake as a function of time, concentration, duration and type of preexposure to light was determined in two cultured Chinese hamster ovary cell lines. One cell line lacks the transferrin receptor. In the other, the human transferrin receptor has been restored by transfection and is overexpressed constitutively. RESULTS: Although there are some differences in pattern of stimulation of uptake, nifedipine subjected to either UV or fluorescent light strongly promotes the uptake of 67Ga in the cultured cells in a time-dependent and concentration-dependent manner. Maximal uptake of 67Ga occurs when the cells are incubated for 30 min with 25 micromol/L nifedipine preexposed to either 4h of fluorescent or 1h of UV light. Under these conditions, uptake of 67Ga is 1000-fold greater than basal levels and 50-fold greater than can be achieved by the transferrin-dependent route. Light-shielded nifedipine has no effect on 67Ga uptake. CONCLUSION: The effect of photodegraded nifedipine on the uptake of 67Ga is independent of expression of the transferrin receptor. The potential for photodegraded nifedipine to improve oncologic imaging with 67Ga warrants further investigation.