Filters

One item frequently neglected, when researchers report on the room light used for testing, is whether the fixture did or did not have a diffuser. This one item can affect the SPD of the radiation source very dramatically as illustrated in Figure 2, taken from a publication of Cole and associates.34 Many have probably personally experienced this same phenomena. The absorption of UV rays by the plastic sandwiched between the glass of windshields, accounts for why photochromic lenses do not work...

N

Indomethacin (13) is quite photostable in the solid state (7.5 decomposition after 72 h irradiation)32 but reacts in solution.18 In methanol the usual decarboxylation is the main process33- 34 when mercury lamps are used, while daylight irradiation leads to products conserving the carboxyl group which have been rationalised as arising via the acyl radical (Scheme 6).35 In the case of the related drug 2-(2,6-dichlorophenylamino)phenylacetic acid (diclofenac, 14), on the other hand,...

Chemical Actinometers

Chemical actinometers are systems undergoing a photochemical process with an accurately known quantum yield the photochemical conversion is directly related to the number of photons absorbed. Thus, the determination of absolute intensities, that is, number of photons incident onto the sample, is one of the main advantages of chemical actinometers. In addition, the detector is generally cheap allowing easy replacement in case of damage. There are no geometry problems the actinometric system can...

Experimental

PABA and Benzophenone-8 were obtained from TCI America, Padimate-O, Benzo-phenone-3, Octocrylene, Octylmethoxycinnamate, and Octylsalicylate were obtained from ISP Van Dyk. Parsol-1789 was obtained from Givaudan. Menthyl anthranilate and valerophenone were obtained from Aldrich. Acetonitrile was obtained from Burdick and Jackson. All reagents used were of the highest purity available and were used as received. Solar simulators are designed and constructed to provide illumination with a spectral...

Kjo

There is no reason to expect that the primary process is different in the solid, but there the radicals cannot migrate, and thus recombine to the starting material. Therefore, the solid is rather photostable under anaerobic conditions. On the other hand, when oxygen is present in the atmosphere, it adds to the radicals formed at the surface to give peroxy radicals thus making cleavage irreversible and finally leading to various oxidised products such as (295) and (311) (Scheme 85).291 It has...

Materials And Methods

Trans-2-Nitrocinnamaldheyde and quinine monohydrochloride dihydrate were purchased from Fluka Chemie AG (Switzerland) and Aldrich (Italy) respectively potassium ferrioxalate was obtained according to the Hatchard-Parker method.8 Solvents for chromatography were of HPLC grade from Romil LTD (U.K.) deionised double distilled water was used for mobile-phase preparation all other chemicals were of reagent grade. For UV radiation exposure tests two different kinds of light sources were employed 1)...

General

Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 6 November 1996, this guideline is recommended for adoption to the three regulatory parties to ICH. The ICH Harmonised Tripartite Guideline covering the Stability Testing of New Drug Substances and Products (hereafter referred to as the Parent Guideline) notes that light testing should be an integral part of stress testing. This document is an annex to the Parent Guideline and addresses the recommendations for...

Introduction

The study of drug substance degradation under the action of UV visible light is important because it could influence the stability of drug formulations and it could lead to formation of toxic photodegradation products.1-2 In photostability testing of pharmaceuticals, light sources which simulate sunlight or indoor lighting3-4 (according to D65 and ID65 standards) are employed in these exposure tests a standardised method for calibrating the radiation intensity from light sources is required.5...

Photochemistry Of Amiloride

The potassium-sparing diuretic, amiloride, is a basic compound with pKa of 8.7 whereas the major diuretics are weakly acidic compounds. Although it is used almost exclusively in combination with hydrochlorothiazide, there are some reported instances of photosensitivity responses from use of the drug alone.19,20 Amiloride has a strong absorption at 360 nm in the UVA giving it the potential for photochemical action. Additionally, it is susceptible to hydrolytic degradation at elevated...

Photoreactions Of Drugs

Information on drug photoreactivity is probably not sufficient among practitioners of pharmaceutical chemistry. Reports about this topic have been growing in number in the last years, but they are scattered in a variety of journals (oriented towards chemistry, pharmaceutical sciences and techniques, pharmacology, biology and medicine), thus possibly not reaching all interested readers. Furthermore, both the approach used (ranging from the simple assessment of the photolability to detailed...

Recommendations

In Table 6 are listed the most important points to consider when selecting a photon source for pharmaceutical photostability testing. These points were assembled from many of the papers cited. Table 6. Factors to consider when selecting a photon source. Does it have a reproducible SPD Does it cover the entire wavelength range Does its SPD match that of The International Standards Organization (ISO) has developed a standard based on a Toshiba cool white fluorescent lamp, ISO D65 Is the radiation...

Photochemistry Of Triamterene

Photosensitivity responses have been reported for triamterene23 but even though it absorbs strongly in the UVA region at 360 nm, this compound has been found to degrade relatively slowly under UV irradiation. This may be due to the strong fluorescence providing an efficient means of dissipating the absorbed energy. The photodegradation of triamterene led to small amounts of several products which have not been identified at this time. Since triamterene is primarily used in a combination...

Info

This LC-MS method applied to solid-state photostability studies was undertaken to establish not only the nature of the degradants but also any commonality between major metabolic pathways of iV-dealkylation, iV-oxidation, sulphoxidation and hydroxylation. The rate of these in vitro transformations is dependent on the concentration of the substrates, and the formation of the sulphoxides has been proved to be a slow reaction in vitro 5 In spite of previous reports,26 sulphoxidation is identified...

O Oh

This work cannot be detailed here a typical example is the photorearrangement of calciferol (vitamin D2) (273) which undergoes both sigmatropic hydrogen shift to give (274) and electrocyclic ring-closure to give (275) (Scheme 75).254> 255 Obviously vitamins D must be protected from light.256 a-Tocopherol (276) (vitamin E) is well known as an antioxidant. The sensitised photo-oxygenation involves singlet oxygen addition to the phenol moiety giving hydroperoxycyclohexadienone (277). This in...

Phytonadione Photostability

Trans-2-NCA is proposed as a new simple and reproducible actinometer for calibrating the intensity of UV-A radiation from light sources in photostability testing of pharmaceuticals, since it exhibits some interesting properties which allow its use in ICH confirmatory studies. In particular its absorption spectrum covers the full UV-A range, its photodegradation quantum yield over the UV-A range is dependent only on the photons number and not on the radiation wavelength, its photodegradation...

Comparative Investigation Of The Photoinstability Of Local Antimycotics

Figure 9 Photodegradation of topical antimycotics (in lOmg lOOml methanolic solution, Suntest CPS, UVfilter) chlorphenesin , sulbentine , cloxiquine Jft- , tolnaf-tate , naftifine-HCl Figure 9 Photodegradation of topical antimycotics (in lOmg lOOml methanolic solution, Suntest CPS, UVfilter) chlorphenesin , sulbentine , cloxiquine Jft- , tolnaf-tate , naftifine-HCl Figure 10 Degradation products of naftifine HCl in methanolic solution after 30 min irradiation 1.43 min injection peak 6.78 min...

Drug

Scheme 3 General scheme of photosensitization induced by drugs in biological systems. damage. Copper acts at a lower concentration range and its activity is enhanced due to its superoxide dismutase-like activity leading to the scavenging of the superoxide anion. Thus, metal complexation (in certain cases with ligands of biological interest, such as linear and cyclic dipeptides as well as with mono- and di-functionalysed cyclodextrins) exerts an antioxidant activity and a radical blocking action...

Nsaids

Benoxaprofen, Naproxen, Piroxicam, Ketoprofen, Carprofen, Suprofen, Tiaprofenic Acid, Butibufen, Fenbufen, Tolmetin, Benorilate, Bithionol, Phentichlor, Esachlorophen Quinine, Chloroquine, Hydroxychloroquine We are particularly interested in two largely used families of drugs, antibacterial fluoroquinolones and NSAIDs. The former is a modern class of antibiotics, continuously under development with the aim of improving their pharmacological activity and, in the meanwhile, decreasing their...

Oh

The ipecac alkaloid emetine (242), used as antiamebic, is degraded when the dihydrochloride is irradiated in aqueous solution. The observed paths include oxidative cleavage of the methylene bridge between the two heterocyclic rings to give products (243) and (244) as well as oxidation to immonium salt (245) and oxidative cyclisation to (246) (Scheme 69).229 Antimicotics are another class of drugs where many photoreactive compounds are found, among both drugs for systemic and for topical use. A...

Phototoxicity Of Diuretic Drugs In Cell Cultures

The diuretic drugs have been tested for their photoxic potency to a limited extent only. It is generally believed that photosensitizers may induce phototoxic damage at different subcellular locations, but that they have one preferred site of action.24 Yeast and fungus contain only the nuclear target, and were not damaged by UV irradiation with chlorothiazide, hydrochlorothiazide or acetazolamide.25 Photohaemolysis, a test of phototoxic membrane damage, gave positive responses with...

Photostability Problems Of Topical Dosage Forms Of Antimycottcs

The determination of the photoinstability of the drug substance is the first step of the photo-stability testing procedure of drugs. The next one is the investigation of the light sensitivity of the drug substance in its preparation. Antimycotics are often used externally. In many cases it is necessary to determine the photostability of such substances in their topical dosage form. As examples results with natamycin and nystatin will be presented. In methanolic solution the photolysis of...

Iso 105b01

American Association of Textile Chemists and Colorists All of these organizations are in the process of revising their source standards and most of the focus has been on using the procedure found in DIN 53 387 and adopted in ISO standards 4892-1,47 -240 and -3,48 titled, Plastics - Methods of exposure to laboratory light sources. These standards specify not only the total irradiance watts per meter squared but also the percentage of the total distribution or irradiance which must appear in...

Reaction Of The Photoxidation Of Thiazine Ring In Promethazine

Comparative studies in aqueous solutions47 showed that aminopyrine is the most reactive derivative,45 and in general 4-amino substituted pyrazolones react faster than 4-alkyl48 gt 49 derivatives. In the presence of oxygen, photolysis is accompanied by a photo-oxidation reaction.50 The above order of photoreactivity for pyrazolones remains the same in the solid state.51 However, in the latter case different processes may be involved, as with aminopyrine for which the main reaction in the solid...

Detection And Identification Of Photodegradation Products Of Flucytosine And Griseofulvin

Degradation products of drug substances can be responsible for unwanted side effects. Therefore the detection and identification of the degradation products of flucytosine and griseofulvin are of interest Figure 13 . Both are some of the few drug substances used for the systemic therapy of mycotic infections. Flucytosine is orally or parenterally applied for generalised mycoses. 5-Fluorouracil is known as a toxic degradation product of flucytosine. Therefore pharmacopoeias like the Ph. Eur. 97...

Wavelength nm

Figure 3 Absorption spectrum of chloramphenicol in ethanol. Figure 4 Absorption spectrum of chlorpromazine in ethanol. In laser flash photolysis experiments Table 1 direct excitation of CLP produced a Ti state with high efficiency Or 0.52 and a triplet-triplet absorption maximum at 460 nm. The lifetime of the transient was 10 is. No detectable transient was generated from the other compounds under the same conditions. On the other hand, all compounds were able to quench efficiently the lowest...

Photochemistry Of Hydrochlorothiazide

Hydrochlorothiazide A ax 318 nm, emax 32001 mol1 cm1 is a weak absorber compared with frusemide in the region above 300 nm. Nevertheless, it is completely dechlorinated upon irradiation with a medium pressure Hg arc lamp through a glass filter for 5 hours, in deaerated aqueous or alcohol solutions. The quantum yield for dechlorination is 0.18 0.05 under deaerated conditions.5 The thiadiazine ring is liable to hydrolyse in aqueous solution, and the pH-rate profile for the dark hydrolysis has a...

Photoinstability Of Different Substance Groups Of Antimycotics

Bilbnazol Clotrimazol Econazol Fluconazol Isoconazol Ketoconazole Miconazol Oxiconazol Terconazole Tioconazol Griseofulvin Naftifin Sulbentin Tolnaftat 20 40 60 80 content after 2 h irradiation Figure 6 Photoinstability of antimycotics in methanolic solution 2 mg 100 ml with UV-filter 20 40 60 80 content after 2 h irradiation Figure 6 Photoinstability of antimycotics in methanolic solution 2 mg 100 ml with UV-filter The photostability tests have been carried out with the Suntest CPS.6 This...

Conclusions

One of the important consequences that can arise as a result of sunscreen active ingredient photolysis is a loss of absorptivity. This may, in some cases, be significant if the photoproducts do not absorb radiation in the desired wavelength range. In other cases, absorptivity is retained because the photoproduct or products absorb this radiation. For example, Parsol-1789 undergoes photolysis leading to products that have little or no absorptivity in the wavelength region of interest. As a...