Photostability Of Drugs Research Articles

Evaluation of Photostability of Small Molecular Compounds with Solid-state UV Spectra

It is crucial to evaluate the photostability of drugs. However, it requires a longer period of time to evaluate the photodegradation of compounds because extended light exposure to the compound is required to detect photodegradation products with the help of the commonly utilized technique of chromatography. Therefore, a simple and easy approach to estimate the photostability of the compound is required particularly for the initial screening of the drug candidates. It was reported in our previous manuscript that, focusing on ultraviolet-visible (UV/vis) spectrometry, the area under the spectrum curve in the ultraviolet-A (UVA) range (AUSCUVA) are closely related to the photodegradation of indomethacin polymorphs. In this study, the solid-state UV/vis absorption spectra of compound A polymorphs, indomethacin complexes and some small molecule compounds were determined and analyzed to check the applicability of this method. AUSCUVA are closely related to the photodegradation of compound A polymorphs as well as indomethacin. On the contrary, no close relation was observed between AUSCUVA of indomethacin complexes and their photodegradation. Additionally, the result indicated that the differences in their solid-state UV/vis absorption spectra were observed between photosensitive and photostable compounds. Photosensitive compounds show absorption in UVA range, while photostable compounds exhibit less absorption. In conclusion, the solid-state UV/vis absorption spectra of small molecular compounds might provide the key information on the photosensitivity.

Effects of Humactents and Oleogeneous Base in the Photostabilization of Secnidazole Emulgels

This investigation aims to study the formulation of emulgel preparations of secnidazole (SZ, The variables in the composition of the oleaginous phase (liquid paraffin and castor oil) and humectants (propylene glycol and glycerol) and the physical and rheological properties like homogeneity, spreadability, and extrudability were studied. Variations in the viscosity of SZ emulgels were observed due to changes in formulations. The viscosity was central to the stability of the SZ emulgel preparations. SZ is a photosensitive drug, and irradiation formed its primary photodegraded product 2,4-(N-2-hydroxypropyl) diaza-3-methyl-1-nitro-1,5-dione. SZ has been subjected to photolysis by irradiation, and the clear first-order rate constant, kobs, for the degradation of SZ has been determined. The values of kobs (2.79-5.12 × 10-2 min-1) have decreased with the increase in viscosity (20085-29985 cP) of emulgel preparations. The ratio of stabilization is in the range of 2.31-4.22. It is concluded that increasing the viscosity of pharmaceutical preparations may enhance the photostability of light-sensitive drugs.

Photostability and Antiproliferative Activity of Furan Analogues of Combretastatin A-4.

Cancer is one of the most serious health problems that usually require heavy medical treatment. It is important to ensure that no additional burden is placed on patients due to the modes of administration and/or poor quality of pharmaceuticals. In this regard, understanding, quantifying, and improving the photostability (resistance to UV light or sunlight) of drugs is among the important elements that can improve the patient's quality of life. In this work, the photochemical properties of a wide range of furanone analogues of combretastatin A-4 and their antiproliferative activity against A-431 epidermoid carcinoma cells were studied in a search for compounds with improved photostability and antiproliferative activity. It was found that the incorporation of an arylidene moiety led to a significant improvement in photostability, while the antiproliferative activity strongly depends on the nature of the aryl residue in the arylidene moiety. The high photostability of arylidenes was achieved due to the delocalization of the central double bond of the 1,3,5-hexatriene system, which limited the 6π-electrocyclization. The best results in terms of antiproliferative activity were obtained for thiophene arylidene (IC50 = 0.6 μM) and 3,4-diarylfuran (IC50 = 0.047 μM). The obtained results address the lack of data available now in scientific literature on the photodegradation of combretastatin A-4 analogues and should be taken into account in studies of the side effects of pharmaceuticals based on them.

Photostability of Topical Agents Applied to the Skin: A Review.

Topical treatment modalities have multiple advantages starting with the convenient application and non-invasive treatment and ending with the reduction of the risk of the systemic side effects. Active pharmaceutical substances must reach the desired concentration at the target site in order to produce a particular therapeutic effect. In contrast to other dosage forms topical agents applied to the skin may also be susceptible to photodegradation after application. That is why the knowledge of the susceptibility of these topical drugs to UV irradiation, which may contribute to their degradation or changes in chemical structure, is very important. Active pharmaceutical substances used in dermatology may differ both in chemical structure and photostability. Furthermore, various factors—such as light intensity and wavelength, pH, temperature, concentration—can influence the photodegradation process, which is reflected in particular in kinetics of photodegradation of active pharmaceutical substances as well as both the quantitative and qualitative composition of by-products. The aim of this study was to conduct a systematic review of the photostability of dermatological drugs, as well as of other substances commonly applied topically. The photostability of glucocorticosteroids, retinoids, and antifungal drugs as well as non-steroidal anti-inflammatory drugs applied topically and selected UV-filters have been discussed. Furthermore, the impact of photoinstability on the effectiveness of pharmacotherapy and some photostabilization strategies have been also included.

Photostability of Terbinafine Under UVA Irradiation: The Effect of UV Absorbers.

The photostability of drugs administered topically on unprotected skin is a complex phenomenon that could be connected with the loss of activity or, rather rarely, the occurrence of toxic degradation products. In this study, an in-depth investigation of the photostability of terbinafine, in both solutions and formulations, was conducted, taking into account the presence of UV absorbers such as TiO2 , ZnO, avobenzone, 3-(4-methylbenzylidene)camphor, octocrylene, benzophenone-1 and benzophenone-2. The clear photocatalytic degradation of terbinafine in ethanol solution was observed in the presence of TiO2 and/or ZnO. In other cases, terbinafine was stable, with the exception of, in the presence of octocrylene. The presumed degradation products of terbinafine were identified for the first time using LC/MS/MS, and transformation pathways were proposed. In the case of a cream formulation, the percentage of initial terbinafine content was almost unchanged in the presence of the UV absorbers benzophenone-1, benzophenone-2 and 3-(4-methylbenzylidene)camphor. In vitro cytotoxicity risk assessment of terbinafine based on photostability under UVA irradiation was evaluated using the human skin fibroblast BJ (ATCC® CRL-2522™), and this showed no statistically significant difference in cell viability for all samples analyzed.

A photochemical approach for evaluating the reactivity of substituted lappaconitines

Lappaconitine (LC) is a natural diterpenoid alkaloid (DTA), acting as a human heart sodium channel blocker and possessing a wide range of biological activities, the cellular and molecular mechanisms of which are widely studied. This interest is due to the fact that various representatives of this DTA class show opposite biological activities. The possible reasons for this difference seem to be related to the peculiarities of the substituent effect on the drug-receptor binding process. In this work, the influence of substituents on the reactivity of LC and its derivatives has been studied by using elementary processes of photodecomposition. The given approach includes the joint analysis of the photophysical properties of the studied systems and their photodecomposition quantum yields. It allows us to trace the influence of substituents, located in the diterpenoid skeleton and anthranilic fragment, on processes in both moieties of LC. Summarizing the data obtained, an inverse dependence of fluorescence and photodegradation quantum yields has been observed. This correlation established for LCs, in particular, allows one to propose a way to evaluate the photostability of potential drugs based on fluorescence analysis. This would be appropriate for compounds in which the reactivity depends on intersystem crossing, i.e. in the cases where the initial and reacting excited states differ in multiplicity.

Separate and simultaneous binding of tamoxifen and estradiol to human serum albumin: Spectroscopic and molecular modeling investigations

In the recent years, tamoxifen has been often co-administrated with estradiol to treatment of breast cancer. Hence, we examined the interaction of two anti-breast cancer drugs, tamoxifen and estradiol, with human serum albumin (HSA) using spectroscopic and molecular modeling techniques. The quenching of intrinsic fluorescence and docking were used to calculate binding affinity and location, while the RLS, synchronous fluorescence and CD spectroscopy were done to investigate the effect of these drugs on protein conformational changes, both separately and simultaneously. While the photo-stability of drugs increased in the presence HSA, the enhancement of RLS intensity was attributed to the formation of a new complex between the two drugs and the protein. Both drugs showed a strong ability to quench the fluorescence of HSA via static mechanism. The fluorescence quenching action at different temperatures and enhancement of RLS intensity were much stronger when the two drugs co-existed, whereas the binding affinity of both drugs were partially affected by each other, which demonstrate that two drugs bind to distinct/different location on HSA via hydrophobic interactions. On the other hand, appearance of new peak at 405nm accompanying with quenching of HSA fluorescence at 340nm by tamoxifen revealed that the drug binds near the protein Trp residue in subdomain IIA, which confirmed the docking results. Furthermore, synchronous fluorescence and CD data clearly indicate that the conformation of HSA was changed upon addition of the drugs which can affect the physiological functions of HSA and binding of other drugs.

Photostability and Photostabilization of Drugs and Drug Products

Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions. The various modes of photodegradation of drugs with examples of selected compounds are presented. The biological consequences of the effect of light on the drug degradation are described. The photostability testing of drugs and drug products and the requirements under ICH guideline are discussed. Some information on the packaging requirements for the formulated products is provided. The various methods used for the photostabilization of solid and liquid dosage forms are also discussed.

Improving drug biological effects by encapsulation into polymeric nanocapsules.

This review is based on selected reports from 2004 to 2014 and provides a comprehensive and updated overview of the state of the art related to the drug delivery advantages of polymeric nanocapsules, which are a specific type of polymeric nanoparticles used for improvement of biological effects. Special attention is given to the application of nanocapsules to increase the chemical and photostability of drugs, to modulate the interaction with cells and tissues, to reduce adverse effects of drugs, and to increase the drug efficiency and/or bioavailability. Moreover, this review covers in vitro and in vivo studies, highlighting interesting examples of drugs from several therapeutic classes for which efficacy is improved by encapsulation in different types of nanocapsules, especially in lipid-core nanocapsules. We also briefly present the first results obtained so far attesting to the safety of using polymeric nanocapsules for drug delivery.

Promethazine-montmorillonite inclusion complex to enhance drug photostability.

The capability of montmorillonite as a matrix (MONT) to improve the photostability of photolabile drugs has been recently reported. Herein promethazine (PRO), which was chosen as a model drug because of its photodegradation mechanism, was intercalated into this inorganic matrix, and the effects on drug photoprotection were evaluated as well. The hybrid material (MONT-PRO) was successfully prepared with high drug loading and then was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and FTIR spectroscopy. The spectrophotometric measurements as a function of light exposure time showed that PRO intercalation into montmorillonite markedly improved the drug photostability because a 5-fold-slower degradation rate was determined compared to that measured for PRO in homogeneous solutions; nanosecond transient absorption measurements highlighted that the interaction with the inorganic matrix made negligible the photoionization process of the drug, and its efficiency in producing singlet oxygen was strongly reduced. The MONT-PRO intercalation compound could be easily formulated in gel or ointment media without losing its photostability.

Implications of In-Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 1: Drug Products Administered by Injection

Basic guidance on the photostability testing of pharmaceuticals, designed to cover manufacturing and storage over shelf life, has long been established within ICH Q1(ICH,B(10) , but the guideline does not cover the photostability of drugs during or after administration (i.e., under conditions of use). To date, there has been a paucity of guidance covering the additional testing that would be of value during the clinical preparation and use of products. This commentary suggests a systematic approach, based on realistic "worst case" photoexposure scenarios and the existing ICH Option 1 and 2 light sources, to provide valuable data to pharmaceutical manufacturers and compounding pharmacists for the safe and effective use of photosensitive injection products.

Ultrafast Photodynamics of Drugs in Nanocavities: Cyclodextrins and Human Serum Albumin Protein

In this feature article, we discuss recent advances in studying ultrafast dynamic and structural aspects of host-guest interactions. Steady-state and time-resolved techniques exploring events from the femto- to nanosecond regime were used to examine the ultrafast photodynamics and subsequent events in selected nanostructures of the formed complexes. These consist of aromatic systems, biologically relevant molecules, and drugs trapped within cyclodextrins (CD) and human serum albumin (HSA) protein pockets. We examine the effects exerted by these chemical and biological cavitands on internal twisting motions, proton transfer and charge transfer, and cis-trans isomerization reactions that may occur in the confined molecular systems. In addition, the influence of a restricting environment on the interaction of guest molecules with biological water is considered. The dynamic details of the complexes (diffusion, early interactions, formation, stability, internal guest diffusion, and conformational changes) and the excited-state relaxation pathways, rate constants of the involved processes, and changes in the electronic distribution within encapsulated guests gave clues to elucidate their photobehavior and are relevant to the photostability and delivery of drugs when using nanocarriers.

Quantitative Design for Photostabilization of Nifedipine by using Titanium Dioxide and/or Tartrazine as Colourants in Model Film Coating Systems

The photostabilization of nifedipine by using film coating has been investigated in model systems in which a drug sample, dispersed on a glass plate, was covered with a free film and exposed to intensive light of mercury vapour lamp. The light transmission properties of films containing titanium dioxide or tartrazine alone as colourant were not always satisfactory. The tartrazine system exhibited superior light transmission properties to the titanium dioxide system at all additive concentrations. However, in combination both colourants gave much better light protection than did the colourants separately. The film-coated drug degraded following apparent first-order kinetics. The degradation rate constant decreased as both colourant concentration and film thickness increased; thus photostabilization was almost completely achieved by applying a film (thickness: 60 microns) of the binary mixture system containing only 0.7% of each of these colourants. The protective effectiveness of a film could be quantitatively evaluated by plotting the degradation rate constant against CL value of film formulation (C: concentration of colourant; L: film thickness). The degradation rate constant showed a good linear correlation with the average percent transmittance of a film in the wavelength range relating to the photolytic degradation of the drug. The average percent transmittance was thus proved to be an important and useful parameter for estimating the photostability of film-coated drugs.

A Critical Assessment of the ICH Guideline on Photostability Testing of New Drug Substances and Products (Q1B): Recommendation for Revision

The ICH guideline on photostability (ICH Topic Q1B) was published in November 1996 and has been implemented in all three regions (US, EU, and Japan). The guideline describes a useful basic protocol for testing of new drug substances and associated drug products for manufacturing, storage, and distribution, but it does not cover the photostability of drugs under conditions of patient use. The pharmaceutical industry now has considerable experience in designing and carrying out photostability studies within the context of this guideline, and issues have been identified that would benefit from the revision process. The purpose of this commentary is to accomplish the following: (i) highlight issues proposed for consideration in the ICH revision process, (ii) offer a rationale for why these issues may compromise the design of a testing protocol and/or the results of the testing program, and (iii) provide recommendations for clarification of the guideline.

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.

Photostability of drugs: photodegradation of melatonin and its determination in commercial formulations

The photostability of melatonin, a hormone used as supplementary drug in the alleviation of jet-lag and other sleep disorders, was studied. The drug photodegradation at different pH values was monitored by HPLC methods. The main photoproduct was isolated and characterised on the basis of the NMR, FTIR, and mass spectra. A HPLC method, in combination with a post-column on-line photochemical derivatisation was developed for the selective and reliable quality control of commercially available melatonin containing products.

Book Review: Photostability of Drugs and Drug Formulations

Book Review: Photostability of Drugs and Drug Formulations

Photo-Stability of Drugs in Enteral Hyperalimentation Solutions and Its Influence on the Dose Given by a Continuous Infusion.

Enteral hyperalimentation (EH) has been getting popular as one of the ways for hyperalimentation.Administration of EH solution requires a couple of hours (up to about 4 hrs) to be completed.Therefore, drugs in EH solutions must be stable during administration.Several studies on the stability of drugs in solutions such as physiological saline and 5% glucose for an intravenous infusion have been reported Recent study on photostability of a drug in 5% glucose solution in a ward showed that administration of unstable drug by a continuous infusion resulted in a significant loss of close. Simulation study also showed the influence of unstability of drug on the dose given by a continuous infusion. However, stability of drugs in EH solutions has not been reported yet.In this report, we studied photo-stability of drugs in EH solutions, which is turbid, and assesed the influence of unstability of.drug on the dose given by a continuous infusion.For this study, Clinimeal (CM) and Besvion (BV) were selected as products for EH, and vitamin B2 and vitamin B12, as photounstable drugs.