Nifedipine tablets

Varshosaz, J., and Z. Dehghan. 2002. Development and characterization of buccoadhesive nifedipine tablets. Eur J Pharm Biopharm 54 135. 

Q. R Cao, H. G. Choi, D. C. Kim, and B. J. Lee. Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose Effect of coating conditions. Int. J. Pharma. 274 107—117, 2004. 

Remunan C, Bretal MJ, Nunez A, Jato JLY. Accelerated stability study of sustained-release nifedipine tablets prepared with Gelucire. Int J Pharm 1992 80 151-159. 

Thoma K, Aman W. Influence of Blister Golouration on the PhotostabUity of Nifedipine Tablets 15th Pharmaceutical Technology Gonference, Oxford, U.K., March 19th-21st, 1996, Kongreband. Vol. 3 114-127. 

The influence of variations in the film layer thickness on photo protection was investigated using uncoated nifedipine tablets. Samples of the tablets were completely covered with yellow transparent blister films of layer thicknesses ranging from 30-300 pm. The photostabilizing effect of the yellow blister film was found to increase with film layer thickness. After six hours irradiation the loss of drug content was 24% for the 30 pm films and only 6% for the 300 pm films, (Fig. 6) a substantial improvement in the photo protection of the product (21). 

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 6 Influence of the film thickness of yellow transparent blister films on the photostability of uncoated nifedipine tablets 20mg (Suntest CPS+, 720 W/m, UV filter). ( ) 300pm, (o) 200pm, ( ) 150 pm, ( ) 70 pm, ( ) 30 pm. Source. From Ref. 21.

Blue and colorless blisters had little photo protective effect on nifedipine tablets. Therefore, it is evident that the use of a blister of the proper color can be an effective photo protecting measure, but only if its absorption spectrum corresponds to that of the drug substance/product (Fig. 8) (20). 

Figure 7 Content of the nifedipine degradation product (nitrosophenylpyridine) in 13 coated nifedipine tablet commercial products after irradiation inside or outside of the blister packaging (Novasoitesf " 72 hours). ( ) With blister, ( ) without blister. Source. From Ref. 11.

Tablets can also be photostabilized using aluminum blister packs. This photostabilization method is used by some nifedipine tablet manufacturers. Nifedipine tablets packaged in aluminum foil unit dose blisters do not require any additional photo protection (e.g., coating), providing a significant saving in development and manufacturing costs as well as stability testing (40).

Thoma K, Aman W. The influence of blister colouration on the photostability of nifedipine tablets. 15th Pharmaceutical Technology Conference, Oxford, UK, March 19-21,... 

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.

Besides UV absorbers and food colorants, use of opacifiers is another way of photostabilizing photosensitive tablets. The protecting effect of yellow, red and black iron oxide could be shown for tablets containing the antiviral drug sorivudine, as well as molsidomine and nifedipine tablets (15). Iron oxides were found to be more effective than titanium dioxide, especially if the drug is particularly sensitive to radiation of wavelengths between 400 and 420 nm (e.g., nifedipine), where titanium dioxide shows an "absorption gap" (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 difference found between the two nifedipine tablet formulations in Table 82 stems from the way in which the coprecipitate is produced. In Formulation No. 1 it is produced separately and subsequently pressed together with a further granulate. In Formulation No. 2, the coprecipitate is formed on the surface of the cellu-... 

Table 82. Nifedipine tablets made from coprecipitates with povidone [240 b]...

Nicotinic Acid Tablets (200 mg) Nicotinamide see Vitamin B3 Nifedipine Tablet Cores (10 mg) Nitrendipine Tablets (25 mg) Nitrofurantoin Tablet Cores (100 mg) Nitrofurantoin Tablets (100 mg) Norephedrine Syrup (40 mg/10 g) Nystatin Suspension (100,000 i.u./ml) Nystatin Tabet Cores (200 mg) Nystatin Tablets (50 mg and 100 mg)... 

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). 

A patient developed hypotension and severe bradycardia on two occasions after being given her usual antihypertensive medication of labetalol and extended-release nifedipine crushed and given via a nasogastric tube. Crushing the nifedipine tablet altered its release characteristics so that the... 

Fig. 4.3 Particle size variation in the manually (in a mortar with a pestle) crushed Nifedipine tablet (Adalat 10 mg retard). Scale bar in SEM is 100 pm [29]...

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