Nifedipine, photodegradation

Marciniec, B. and Rychcik, W., 1994, Kinetic analysis of nifedipine photodegradation in the solid state, Pharmazie 49, 894-897. 

With UV detection at 237 nm, the total peak area (i.e., sum of the peak areas of nifedipine and its oxidation product) decreased throughout the photodegradation of the nifedipine sample. For example, the total UV peak area after 6 hr was only 65% of its initial value, suggesting a mass balance deficit. However, the total peak area by CLND was consistent throughout, with an overall RSD of 2.5%. Thus, the CLND indicated that the decrease in total UV peak area was due to different RRF values for the two compounds. Furthermore, the RRF value for the oxidation product was readily calculated using Eq. (2) RRF237 nm = 0.534 on a weight basis. 

Figure 8 Photodegradation of nifedipine as monitored by HPLC/UV. HPLC conditions Zorbax Rx-C18, 0.21x15 cm mobile phase 60/40 MeOH/H20, 0.2mL/min 5 pL inj. Detection UV = 237nm. Arrows indicate the progression of peak areas with time.

Table 1 Mass Balance of Photodegraded Nifedipine Before and After RRF Correction from CLND Data... 

Thoma K, Kerker R. Photodegradation and photostabilization of nifedipine in dosage forms. Pharm Ind 1992 54 359-365. 

Thoma K, Kubler N. Photodegradation of quinolones. Pharmazie 1997 52(7) 519-529. Thoma K, Klimek R. StabUittsspezifische polarographische gehaltsbestimmung von nifedipin in arzneUormen. Dtsch Apoth Ztg 1980 120 1967-1972. 

Figure 4 Effect of wavelength on the photodegradation of (0), nifedipine ( ), nitroso-derivative (A) nitro-derivative.

Differential scanning calorimetry is a technique that has recently been used for the detection of photodegradation products in solid drug substances. Even minor amounts of degradation product within a crystal lattice can provoke a significant decrease in its melting point. This method has successfully been used to monitor the photostability of nifedipine (15). 

Another investigation of nifedipine tablet commercials demonstrated the photo protective effect of colored blisters (11). The photodegradation of coated nifedipine tablets was decreased from a maximum of slightly more than 5% to a maximum of 2% by use of a colored blister pack. The photo testing used was equivalent to a four- to six-week daylight exposure behind window glass (Fig. 7). 

Figure 8 Influence of the blister coloration on the photodegradation of uncoated nifedipine tablets 20 mg (Suntest CPS+, 720 W/m, UV filter), (t) green blister, (v) blue blister, ( ) yellow blister, (o) colorless blister absorbing UV-light, (a) red blister, (a) colorless blister, ( ) orange blister, ( ) without blister. Source. From Ref. 20.

Due to absorption of incident radiation in upper layers, the drug itself may have a photostabilizing effect. Photodegradation often leads to the production of colored products which themselves absorb and further shield the sample. Consequentially, degradation rates decrease with increasing concentrations as shown by the example of nifedipine solutions (Fig. 1) (3). 

Figure 1 Influence of the initial concentration of active in solution on the photodegradation of nifedipine (Spectrotest, filter 700 to 417nm, depth of solution 4.8cm). ( ) 300mg/100mL,...

Figure 2 Influence of the total drug content of similarly sized tablets on the photodegradation (Suntest CPS+). (A) Nifedipine tablets (720 Nlrrf, UV special glass filter), ( ) 20mg, (A) lOmg, ( ) 4mg. (B) Molsidomine tablets (415W/m, window glass filter), ( ) 20mg, (A) 8mg, ( ) 4mg. [Thoma K, Aman W. In preparation].

Figure 3 Influence of and sampling depth on the noted percentage photodegradation of nifedipine and molsidomine tablets. ( ) Nifedipine tablets (Suntest CPS-i-, 720 W/m, UV special filter, 12hours). ( ) Molsidomine tablets (Suntest CPS+, 415W/m, UV special filter,...

In contrast, penetration into solids is normally restricted to a depth much less than 1mm. Only the top most layers of nifedipine and molsidomine tablets showed photodegradation (Thoma K, Aman W. In preparation) (4). This can easily be seen with nifedipine tablets where photodegradation results in coloration. After 12 hours, in samples stored in a photostability testing cabinet, no further degradation could be observed, as shown in Figure 3. Microscopic examination of these samples showed this coloration was restricted to a depth of less than 400 pm, as shown in the microphotograph of Figure 4. 

Figure 4 Cross-section of an irradiated 20mg nifedipine tablet showing the visual depth of photodegradation (bi-convex, 6mm diameter) (Suntest CPS-h, 12hours, 720W/m, UV special filter). Source From Ret. 4.

The impact of the surface area can also be shown by the fact that once a formulation is pressed into tablets, little difference between the particle sizes of the drug compound is evident, as then the surface area of the tablet becomes more important. Figure 7 shows the comparison of two different sizes of nifedipine active and tablets produced using these materials. This comparison also reveals a decrease in the photodegradation rate, which can be attributed to the decrease in the drug surface exposed to incident radiation. Similar results were obtained with molsidomine (Thoma K, Aman W. In preparation) (4). 

Investigations, related to the photoprotection of nifedipine tablets using films containing titanium dioxide and/or tartrazine, revealed that the photoprotective effect of a film could be evaluated by using its concentration of colorant (C) and thickness (L) value. This value is the product of concentration of the colorant C and the film thickness L. Tablets coated with films having the same CL value had the same photodegradation rates. Degradation rates were found to be proportional to the CL value for every colorant system tested (18). 

Another example, which demonstrates the importance of the spectral overlay principle, is the fact that film coatings containing titanium dioxide provide sufficient protection for molsidomine (Thoma K, Aman W. In preparation) (4), whereas nifedipine tablets coated with such films still show photodegradation (19). 

The dielectric constant of a solvent plays a significant role in solubility and stability of the solute. Few studies relating to the dielectric constant of the solvent medium to the photodegradation rate have been undertaken. Thoma and Klimek (8) reported that the improvement in the photostability of nifedipine noted by them is due to an increase in dielectric constant in both ethanol/water and propylene glycol/water mixtures. 

Thoma and Klimek (8) found that the photodegradation of nifedipine in solution was greatly influenced by photon intensity and wavelength. Nifedipine was found to be photolabile at longer wavelengths of UV and in VIS radiation. 

Vargas F, Rivas C, Machado R. Photodegradation of nifedipine under aerobic conditions. Evidence of formation of singlet oxygen and radical intermediate. J Pharm Sci 1992 8(4) 399-400. 

Oral liquids of very photosensitive drugs such as molsidomine and nifedipine are compromised by photodegradation during administration even in short exposure. For safety reasons and in view of its high photosensitivity, molsidomine oral liquid was withdrawn from the market. 

Hayase, N., Itagaki, Y., Ogawawa, S., Akutsu, S., Inagaki, S., and Abiko, Y., 1994, Newly discovered photodegradation products of nifedipine in hospital prescriptions, J. Pharm. Sci. 83, 532-538. 

Various techniques have been applied in studies of solid samples. A direct method based on infrared spectroscopy has been used in the study of pharmacologically active compounds such as nitroimidazole derivatives (chemotherapeutics) and nifedipine (Marciniec and Rychcik, 1994 Marciniec et al., 1997). This approach can be applied in kinetic and quantitative examinations of the degradation process. An alternative method based on diffuse reflectance spectrophotometry takes into account the surface reflectance of the sample (Zhan et al., 1995). In recent years, Raman spectroscopy has become a powerful tool for the study of various processes in the solid state. The technique allows mapping of the concentration of one specific component within a sample, e.g., an active ingredient in a tablet formulation. This method may therefore become a useful tool in future studies of solid-state photodegradation (Opel and Venturini, 2002). 

Logan, B.K. and Patrick, K.S. (1990) Photodegradation of nifedipine relative to nitrendipine evaluated by liquid and gas chromatography, J. Chromatogr., 529, 175-181. 

Scheme 55. Photodegradation leading to dehydrogenation of nifedipine, reserpine, and nicardipine.

Figure 88. Effect of light intensity on the photodegradation of nifedipine at room temperature. Light source , high-pressure mercury lamp sunlight , fluorescent lamp. (Reproduced from Ref. 403 with permission.)...

As shown in Fig. 88, the amount of photodegraded nifedipine was proportional to the number of incident photons.403 Maximum photodegradation of nifedipine in tablets occurred at 420 nm (Fig. 89).404 On the other hand, the relationship between the discoloration rate of sulfisomidine in tablets irradiated by a mercury lamp versus ultraviolet light intensity was complex.405 The values of L, a, and b determined for the discoloration of the tablet depended on the energy of the mercury lamp.406 Photodegradation of menatetrenon yielded linear plots of log k versus the reciprocal of the illumination intensity, as shown in Fig. 90.407... 

Figure 89. Wavelength dependence of photodegradation of nifedipine tablets at 15°C. Light intensity 1.23 x 10 erg/cm2. (Reproduced from Ref. 404 with permission.)...

I. Sugimoto, K. Tohgo, K. Sasaki, H. Nakagawa, Y. Matsuda, and R. Masahara, Wavelength dependency of the photodegradation of nifedipine tablets [in Japanese], Yakugaku Zasshi 101, 1149-1153(1981). 

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