Photostability Testing Research Articles

Concurrent Enhancement of Curcumin's Stability and Dissolution by the Preparation of its Eutectic Mixtures

Rhizomes of Curcuma longa is the source of the chemical curcumin. It possesses several pharmacological characteristics, including anti-inflammatory, anti-hyperlipidemic antioxidant properties. But it also has several drawbacks, that limit its application as a medication. Curcumin's drawbacks that impede its application as a therapy include its poor chemical instability, solubility, bioavailability, and quick systemic clearance because of its rapid metabolism under physiological conditions. Its weak internal physicochemical properties make it less effective. These characteristics include photoinstability, limited bioavailability due to hydrolysis, and water insolubility. For the purpose of this investigation, a eutectic combination of 15% and 85% curcumin and nicotinamide was made. DSC, FTIR, and XRD analyses were used to assess the product's dissolving rate and photostability. The eutectic combination dissolved ten times faster after forty minutes than the parent medication. Following the 7th s day of accelerated photostability testing, curcumin-nicotinamide eutectic combinations shown 36% degradation, which was 34% less than pure curcumin. The photostability nvestigations were carried out in accordance with ICH Q1B recommendations. According to current research, cucumin may be a viable contender for pharmaceuticals in the future

Investigation of aclidinium bromide degradation by stability-indicating HPLC methods, characterization of impurities by NMR, and identification of degradation products by LC-MS

Aclidinium bromide (ACL) is a long-acting muscarinic receptor antagonist used for the long-term treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the degradation of aclidinium bromide under stress and stability testing conditions, for which we developed and validated the first stability-indicating, specific, precise, accurate, and robust assay and related substances HPLC methods. Nine of the compounds used as reference standards were synthesized and fully characterized by 1H and 13C NMR, MS, and FTIR techniques. Two of these molecules, namely ACL-dimer and ACL-desphenyl, are novel compounds and reported herein for the first time. Hydrolysis of aclidinium resulted in major degradation via the formation of ACL-desDTG and DTGA metabolites. ACL-desphenyl and phenol were observed only under oxidative conditions at very low levels (< 0.10%), while ACL-hydroxy, known as a metabolite of aclidinium and confirmed by LC/QDa and LC/Q-TOF m/z data, formed under oxidative stress-testing conditions, UV light, and daylight. The identification of two impurities formed only when aclidinium bromide was treated with hydrogen peroxide was done by LC/QDa and LC/Q-TOF studies and the novel structures were proposed as ACL-bromophenoxy and ACL-bromothiophenyl formed via bromination of the phenyl and thiophene ring on the aclidinium, respectively. The stress and photostability testing studies showed that the aclidinium bromide drug substance is not sensitive to elevated temperature (105 °C, 10 days), slightly sensitive to daylight and UV-radiation, and it showed significant degradation under all hydrolysis and oxidizing conditions. The related substances HPLC method reported herein is also capable to monitor the potential genotoxic impurity 3-bromopropoxybenzene (3-BPB), a class 2 impurity according to ICH M7, and ensures that the impurity remains below the threshold of toxicological concern (TTC) limit, making it safe for patients.

Evaluation of Photostability of Medicines and Development of the Photostabilization of the Photosensitive Medicines

Photo-exposure has a crucial effect on both the quality and quantity of photosensitive pharmaceuticals due to the decrease of their contents or the expression of adverse effects derived from generated photoproducts. The photostability test guidelines (ICH-Q1B, Photostability testing of new drug substances and products) have been established for the photostability evaluation in the new drug application, and obtained results from these tests are required for the elucidation of the final packaging and the dosage form. However, there is no information in the interview form about the photostability of medicines that are taken out from a press through package (PTP) sheet and their dosage forms are changed for the purpose of the improvement of medication compliance of patients. It is an important issue to clarify the photostability of medicines that are crushed or suspended and determine the potential photoproducts for safe use. Herein, in this review, results of the evaluation of the photodegradability of photosensitive active pharmaceutical ingredients (APIs) and their formulations, the determination of several photoproducts generated by ultraviolet-light (UV) irradiation and the development of photostabilization strategy for them based on the addition of several photostabilizers are summarized.

Telmisartan Tablets Repackaged into Dose Administration Aids: Physicochemical Stability under Tropical Conditions.

Dose administration aids (DAAs) are commonly used to assist patients with chronic disease to manage multiple medications and thus improve adherence. Several brands of telmisartan, commonly prescribed for hypertension, are available in Australia. Manufacturer’s storage advice is to leave tablets in the blister strip until administered to patients. This study aimed to investigate the stability of telmisartan tablets when repackaged and stored in DAAs, to identify a brand, which is sufficiently stable to be repackaged. All available brands of telmisartan tablets in Australia, which contain different excipients, were repackaged into DAAs and stored at 30 °C, 75% RH for 28 days before screening, using visual inspection and physical testing. A candidate brand was then selected for physicochemical and photostability testing using pharmacopoeial methods. Repackaged Mizart® tablets were shown to be sufficiently stable, when repackaged and stored under tropical conditions (30 °C, 75% RH) for 28 days. Several of the other brands were deemed inappropriate for repackaging, due to physical instability, highlighting the importance of considering not only the drug, but also excipients to ensure the stability of repackaged medicines. Although the repackaging of telmisartan tablets is not advised, this study provides evidence to support the Mizart® brand as an option for pharmacists to recommend for repackaging.

610 Development of a natural product-based sunscreen

Sunscreens are a cornerstone of skin cancer prevention; however, currently available sunscreens have limitations. Concerns regarding current organic sunscreen agents include photodegradation, potential disruption of endocrine pathways, and paradoxical generation of damaging reactive oxygen species (ROS). Recent studies by the FDA have shown that organic sunscreens permeate into systemic circulation at levels warranting further safety testing, highlighting the importance of investigating alternative strategies for safe and effective photoprotection. Towards this goal, we previously conducted high-throughput screening of natural compounds for photoprotective potential, quantifying UV spectral absorbance, photostability, cytotoxicity, and ROS generation. From a pilot set of 915 compounds, we prioritized 11 candidates of interest for confirmatory photostability testing and follow-on in vitro SPF testing at 5wt% in P2 formulation. Top performers were diosmin (DIO; SPF 2.7), isoliquiritigenin (IQL; SPF 2.5), ferulic acid (FA; SPF 3.1), and cytisine (CYT; SPF 6.3). To create a broad-spectrum formulation, these agents were assessed individually and in combination for in vitro SPF and critical wavelength (λcrit), and in vivo in C57BL/6J mice for protection against ultraviolet radiation (UVR)-induced cyclobutane pyrimidine dimer (CPD) formation and irritant contact dermatitis potential. 10% DIO + 10% FA + 5% CYT was the best performer of our test combinations, with a mean in vitro SPF of 48.6 (SD 3.2), λcrit of 373, and 92.4% CPDs blocked (SD 3.5%). Other promising combinations utilizing varying concentrations of FA and CYT with DIO or IQL also demonstrated λcrit>370 and SPF>15, i.e. the FDA minimum requirements for decreasing the risk of skin cancer. None of the combinations induced irritant dermatitis as assessed by gross and histologic examination after 5 repeated applications to shaved dorsal skin every 2 days. Collectively, these data demonstrate proof of concept for high throughput screening as a method of identifying candidate alternative sunscreen agents toward the formulation of a natural product-based sunscreen.

Photokinetics of Dacarbazine and Nifedipine under polychromatic light irradiation and their application as new reliable actinometers for the ultraviolet range

The photokinetic behaviour of drugs driven by polychromatic light is an area of pharmaceutics that has not received a lot of attention. Most often, such photokinetic data is treated by thermal kinetic models (i.e., the classical 0th-, 1st- or 2nd-order equations). Such models were not analytically derived from the rate-laws of the photodegradation reactions. Polychromatic light kinetic modelling is hence of importance, as a means to providing adequate toolkits and metrics. This paper aims at proposing two reliable drug-actinometers useful for polychromatic UVA range. The general actinometric methodology offered here is also useful for any drugs/materials obeying a primary photoprocess where both reactant and photoproduct absorb the incident light, of the AB{(1Phi )}_{{varepsilon }_{B}ne 0} type. The present method has been consolidated by the η-order kinetics. This framework further demonstrated the lamp-specificity of actinometers. Overall, Dacarbazine and Nifedipine photodegradations obeyed η-order kinetics, and stand as effective actinometers that can be recommended for the ICH Q1b photostability testing.

Photodegradation of Bexarotene and Its Implication for Cytotoxicity.

A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO2 or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (p < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration.

Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium.

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 (w/w) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and Cmax were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability.

Photostability Testing of a Third-Generation Retinoid-Tazarotene in the Presence of UV Absorbers.

Exposure of a drug to UV irradiation could affect its physicochemical properties. Hence, photostability testing is essential for topically administered drugs. Tazarotene, a receptor-selective, third-generation retinoid, is commonly used to treat acne vulgaris and psoriasis. In the present study, an in-depth analysis of the photostability of tazarotene in ethanolic solution in the presence of zinc oxide and/or titanium dioxide as well as benzophenone-type UV filters was performed. Eleven presumed products were derived from the photocatalytic degradation of tazarotene using ultra-performance liquid chromatography–tandem mass spectrometry, and transformation pathways were proposed. The degradation process mainly affected the 4,4-dimethyl-3,4-dihydro-2H-thiopyran moiety. The fragments most susceptible to oxidation were the methyl groups and the sulfur atom. Moreover, in the presence of sulisobenzone, under UV irradiation, tazarotene was subjected to a degradation process, which resulted in two photodecomposition products. In silico studies performed by OSIRIS Property Explorer demonstrated that five of the degradation products could be harmful in terms of the reproductive effects, which are associated with 3,4-dihydro-6-methyl-2H-1-benzothiopyran 1,1-dioxide, while one of them demonstrated potential irritant activity. The cytotoxic properties of the degradation products of tazarotene were assessed by MTT assay on a panel of human adherent cancer cells. Time- and concentration-dependent growth inhibition was evidenced in ovary (A2780) and breast (MDA-MB-231) cancer cell lines. The potential implication of the outcomes of the present research requires further studies mainly concerning the photostability of tazarotene in the topical formulations.

Effect of grape seed extract on skin fibroblasts exposed to UVA light and its photostability in sunscreen formulation.

Grape seed extract (GSE) is rich in polyphenolic compounds, particularly (+)-catechin (C) and (-)-epicatechin (EC). Strong antioxidant activity of these compounds makes GSE to be value-added to the cosmetics with anti-aging properties. However, a lack of stability in different environmental conditions makes GSE challenging for the development of photostable cosmetic sunscreen products. To evaluate photoprotective effects of GSE on human dermal fibroblasts irradiated with UVA light and assess photostability of catechins in cream formulations containing GSE alone or in combination with octyl methoxycinnamate (OMC). MTT assay was used to assess protective effects of GSE on fibroblasts irradiated with UVA light. A photostability of C and EC in GSE and in cream formulation containing GSE was investigated using high-performance liquid chromatography and confirmed by reflection and transmission spectrophotometry using Transpore™ tapes and polymethacrylate (PMMA) plates as substrates. High UVA doses damaged fibroblast structure and inhibited their growth. However, GSE increased cell viability and effectively protected them from UVA damage. Photostability of C and EC was achieved by combination of GSE and OMC that also improved absorption capacity of UV filter and increased overall efficacy of formulation. PMMA plates showed better applicability for in vitro photostability testing of sunscreen formulations. However, despite the instability of Transpore® tape under heat from UV exposure, it can still be economically a substrate of alternative choice for screening. GSE can be used as an effective and sustainable natural resource for prevention of UV-induced skin damage providing long-term protection against premature skin aging.

Photodegradation assessment of amisulpride, doxepin, haloperidol, risperidone, venlafaxine, and zopiclone in bulk drug and in the presence of excipients

Photostability of amisulpride, doxepin, haloperidol, risperidone, venlafaxine, and zopiclone in APIs and powdered tablets during exposure to UVA irradiation was studied. In order to evaluate the photodegradation process an ultrahigh performance liquid chromatography method coupled with tandem mass spectrometry (UHPLC-MS/MS) was developed and validated. It was found that the photodegradation of the studied compounds depends on the type of drug and co-existing excipients. Different percentage of photodegradation of the studied drugs was observed, and therefore amisulpride decomposed at 2.63% in bulk drug and at 5.74% in pharmaceutical preparation, doxepin: 29% and 72.38%, haloperidol: 3.71% and 26.20%, risperidone: 7.13% and 12.86%, venlafaxine: 38.59% and 4.22%, zopiclone: 18.62% and 31.42% respectively, after 114 days of UVA irradiation. In addition, kinetic evaluation of the photodegradation process was performed by determining the order of reaction, reaction rate constant k and time t0.1 and t0.5. The photodegradation products of studied drugs were identified, and their fragmentation pathways, derived from MS/MS data, were proposed. The photostability testing is an integral part of the drug stability assessment to ensure quality, efficacy and safety of the formulated products during manufacturing process, storage as well as normal use.Graphic abstract

Photochemically stabilized formulation of dacarbazine with reduced production of algogenic photodegradants

The present study aimed to develop a photochemically stabilized formulation of dacarbazine [5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; DTIC] for reducing the production of algogenic photodegradant (5-diazoimidazole-4-carboxamide; Diazo-IC). Photochemical properties of DTIC were characterized by UV-visible light spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. A pharmacokinetic study was conducted after intravenous administration of DTIC formulations (1 mg-DTIC/kg) to rats. DTIC exhibited strong absorption in the UVA range, and photoirradiated DTIC exhibited marked ROS generation. Thus, DTIC had high photoreactive potential. After exposure of DTIC (1 mM) to simulated sunlight (250 W/m2) for 3 min, remaining DTIC and yielded Diazo-IC were estimated to be ca. 230 μM and 600 μM, respectively. The addition of radical scavenger (1 mM), including l-ascorbic acid, l-cysteine (Cys), l-histidine, D-mannitol, l-tryptophan, or l-tyrosine, to DTIC (1 mM) could attenuate DTIC photoreactions, and in particular, the addition of Cys to DTIC brought ca. 34% and 86% inhibition of DTIC photodegradation and Diazo-IC photogeneration, respectively. There were no significant differences in the calculated pharmacokinetic parameters of DTIC between DTIC and DTIC with Cys (0.67 mg/kg). From these findings, the supplementary use of Cys would be an effective approach to improve the photostability of DTIC with less production of Diazo-IC.

Effect of photo-degradation on the structure, stability, aggregation, and function of an IgG1 monoclonal antibody

Photostability testing of therapeutic proteins is a critical requirement in the development of biologics. Upon exposure to light, pharmaceutical proteins may undergo a change in structure, stability, and functional properties that could have a potential impact on safety and efficacy. In this work, we studied how exposure to light, according to ICH guidelines, leads to photo-oxidation of a therapeutic IgG1 mAb. We also tested the ability of five different excipients to prevent such oxidation. In samples that were exposed to light, we found that the CH2 domain was considerably destabilized but there were no major changes in the overall structure of the protein. Aggregation of the protein was observed because of light exposure. Mass spectrometry identified that light exposure oxidizes two key methionine residues in the Fc region of the protein. In terms of function, a loss in binding to the neonatal Fc receptor, decreased antibody-dependent cell-mediated cytotoxicity and cell proliferation activities of the protein were seen. Combined analysis of the photo-oxidation effects on the structure, stability, aggregation, and function of the mAb has identified the underlying unifying mechanism. Among the sugars and amino acids tested, methionine was the most effective in protecting mAb against photo-oxidation.

Photostability testing using online reactor HPLC hyphenation and mass spectrometric compound identification illustrated by ketoprofen as model compound

Investigations on the photochemical stability of pharmaceutical substances are mandatory in drug development and licensing as photo-induced degradation of an active pharmaceutical ingredient (API) may not only lead to decreased API concentrations but also to toxic or reactive products. Thus, the US Food and Drug Administration (FDA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) issued Guidance for Industry Q1B “Photostability Testing of New Drug Substances and Products” for testing of pure but also packed drugs. However, photoproducts are also known to be generated in vivo under sunlight exposure of the skin and lead to considerable amounts of adverse drug effects.Herein we present an alternative system that may be used for photostability testing mimicking both situations. It combines a tailored photoreactor with an exchangeable pen light source and a modified HPLC system with online-SPE. Identification of photoproducts may be performed using mass spectrometry. The potential of accurate mass spectrometry as a tool for identification of photoproducts was demonstrated as well. A comparison of the online photoreactor system and the traditional photochamber irradiation was performed using ketoprofen for proof of concept. In both designs acetylbenzophenone and ethylbenzophenone were detected as main photoproducts. The new device allows for fast and easy photostability studies that may help to reduce time consuming in vitro experiments and animal trials. Using state of the art instruments kinetic studies could also easily be performed with qualitative and quantitative perspectives combined into one experimental design with only very low amounts of API needed. This may be useful in early drug development, where only small amounts of API are available. Scale-up may also be easily realized for the generation of reference material for quantification and quality control (QC) processes as well as for toxicity testing.

The impact of ZnO and TiO2 on the stability of clotrimazole under UVA irradiation: Identification of photocatalytic degradation products and in vitro cytotoxicity assessment

In order to ensure the safe and effective use of pharmaceutical products especially for topical administration photostability testing is necessary. The current paper presents an in-depth analysis of the stability of one of the most common antifungal agents, namely clotrimazole. Clotrimazole has proven to be stable under UVA irradiation in applied experimental conditions, but the presence of catalysts such as ZnO and TiO2 has contributed significantly to the degradation of this compound. The findings indicate that its photocatalytic degradation reactions followed the pseudo first-order kinetics with rate constant depending on the pH and the used solvent. Using LC–MS/MS, 14 presumable degradation products of clotrimazole were identified and the plausible transformation pathways were proposed. The in vitro cytotoxicity risk evaluation based on photostability of clotrimazole was also performed using the Human skin fibroblast cell line (BJ) ATCC™ CRL-2522. There was no statistically significant difference between cells viability in all analyzed combinations of clotrimazole, TiO2/ZnO, and UVA irradiation (p<0.05).

Photostability Study on Character and Antioxidant Activity of Tomato Extract (Solanum lycopersicum l.) in Nanostructured Lipid Carrier (NLC) and Conventional Creame

The aim of this study was to investigate the ability of NLC in increasing photostability of tomato extract in term of antioxidant activity. Photostability testing on antioxidant activity of samples were conducted by accelerating method using UVB radiation 32.400 joule for 21 hours radiation. Antioxidant activity was measured by DPPH method. NLC was made by High Shear Homogenization (HPH) method at 24000 rpm for 4 cycles, while conventional creame was made by low speed at 400 rpm. The product were characterized include: pH, viscosity, and particle size. There were had difference characters and physical stability. NLC had smaller size, more homogenous and more stable than conventional creame. It was known that stability of antioxidant activity of tomato extract in NLC system higher than in conventional creame. That was showed with k value, as constanta of rate scavenging activity decreasing in antioxidant power between time (Sigma 2-tail less than 0.005) of NLC and conventional creame were: 2.03x10-2 %/hour ±0.08 (3.94) and 4.71x 10-2 %/ hour ±0.23 (4.88) respectively.

Process optimization and photostability of silymarin nanostructured lipid carriers: effect on UV-irradiated rat skin and SK-MEL 2 cell line.

The objective of the present work was to formulate a novel stable delivery system which would not only overcome the solubility issue of silymarin, but also help to increase the therapeutic value by better permeation, anticancer action and reduced toxicity. This was envisaged through the recent developments in nanotechnology, combined with the activity of the phytoconstituent silymarin. A 2(3) full factorial design based on three independent variables was used for process optimization of nanostructured lipid carriers (NLC). Developed formulations were evaluated on the basis of particle size, morphology, in vitro drug release, photostability and cell line studies. Optimized silymarin-NLC was incorporated into carbopol gel and further assessed for rheological parameters. Stable behaviour in presence of light was proven by photostability testing of formulation. Permeability parameters were significantly higher in NLC as compared to marketed phytosome formulation. The NLC based gel described in this study showed faster onset, and prolonged activity up to 24h and better action against edema as compared to marketed formulation. In case of anticancer activity of silymarin-NLC against SK-MEL 2 cell lines, silymarin-NLC proved to possess anticancer activity in a dose-dependent manner (10-80μM) and induced apoptosis at 80μM in SK-MEL 2 cancer cells. This work documents for the first time that silymarin can be formulated into nanostructured lipoidal carrier system for enhanced permeation, greater stability as well as anticancer activity for skin.

Implications of In-Use Photostability: Proposed Guidance for Photostability Testing and Labeling to Support the Administration of Photosensitive Pharmaceutical Products, Part 3. Oral Drug Products

The ICH Q1B guidance and additional clarifying manuscripts provide the essential information needed to conduct photostability testing for pharmaceutical drug products in the context of manufacturing, packaging, and storage. As the previous 2 papers in this series highlight for drug products administered by injection (part 1) and drug products administered via topical application (part 2), there remains a paucity of guidance and methodological approaches to conducting photostability testing to ensure effective product administration. Part 3 in the series is presented here to provide a similar approach and commentary for photostability testing for oral drug products. The approach taken, as was done previously, is to examine “worst case” photoexposure scenarios in combination with ICH-defined light sources to derive a set of practical experimental approaches to support the safe and effective administration of photosensitive oral drug products.

Stability-Indicating Methods for NSAIDs in Topical Formulations and Photoprotection in Host-Guest Matrices.

Photostability tests applied on topical commercial formulations containing non-steroidal anti-inflammatory drugs have demonstrated a clear degradation of the active compounds when exposed to light. The photodegradation profile of these drugs is usually monitored by spectrophotometric or chromatographic techniques according to the international ICH rules for photostability testing. In the last years, the data are processed ever more by multivariate analysis, as principal component analysis, partial least squares, multivariate curve resolution. These techniques have proved to be able to resolve the complex data sets from evolving chemical processes, by estimating the number of the involved components, their pure spectra and concentration profiles. When applied to the study of drug photodegradation, the multivariate approach has been able to define completely the reaction mechanisms and kinetics parameters. Several novel pharmaceutical formulations have been described to improve the photostability of NSAIDs in topical formulations. The common use of light protective packaging has recently been replaced or supplemented by incorporating suitable excipients in the drug formulations. The addition of UV absorbent agents, deactivating quench reactions that are either singlet oxygen-driven or involve free radicals, has had good success. A clear improvement in the light protection has been shown by entrapping the drugs into supramolecular matrices as cyclodextrins, liposomes, niosomes and other host-guest matrices. The present review gives an updated overview on the stability-indicating methods adopted for a series of NSAIDs in topical formulations and the supramolecular matrices designed to minimize the drug photodegradation.

Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability

The present study aimed to clarify the mechanism of photodegradation of famotidine with riboflavin (FMT/RF), and to develop a photochemically stabilized formulation of FMT/RF. Photochemical properties of RF were characterized by UV-VIS spectral analysis, reactive oxygen species (ROS) assay, and photostability testing. Pharmacokinetic study was conducted in rats after intravenous administration of FMT (1 mg/kg) formulation containing RF (0.01 mg/kg). The UV-VIS spectral pattern of RF partly overlapped with the sunlight spectrum, and ROS generation from photoirradiated RF was remarkable; thus, RF had high photoreactive potential. In the photostability testing, after irradiation (250 W/m2), degradation rate for FMT in FMT/RF was ca. 11-fold higher than that in FMT alone. The addition of radical scavengers to FMT/RF led to attenuated photodegradation of FMT/RF; in particular, the addition of L-ascorbic acid (vitamin C; VC) to FMT/RF showed ca. 86% inhibition of the photodegradation of FMT/RF. The pharmacokinetic study on FMT indicated that the addition of VC (1 mg/kg) to FMT/RF had no significant impact on the pharmacokinetic behavior of FMT. These findings suggest that ROS-mediated photochemical reaction would be involved in the photodegradation pathway of FMT/RF, and the complementary use of VC might be an attractive approach to improve the photostability of FMT/RF.