Investigation of the constituents of commercially available toothpastes.

OBJECTIVES: Toothpaste plays a pivotal role in oral and dental hygiene. This cross-sectional study not only investigates the constituents of toothpastes available in the market and their frequency across different brands but also delves into the potential side effects, irritations, or unfavourable outcomes of these constituents, emphasizing the broader health and environmental implications. METHODS: The largest of the five major chain markets in each district of Istanbul was visited, and adult toothpastes were included in this study. All the constituents that make up the toothpaste were individually recorded in an Excel database. Subsequently, literature regarding the purposes, toxic and potential side effects of each ingredient was gathered using databases such as Google Scholar, PubMed and ScienceDirect. The percentages of these ingredients' occurrence among all the toothpastes were calculated, and the ingredients were categorized into 15 distinct groups based on their usage purposes. RESULTS: There were 160 different varieties of toothpaste belonging to 19 different brands on the market shelves. Although a total of 244 different ingredients were identified, only 78 of them were included in the study. Among the analysed toothpaste types, 105 of them were found to contain 1450 ppm fluoride, whilst 26 toothpaste variants were discovered to have fluoride levels below this value. Among the various ingredients analysed, particular attention was drawn to commonly debated compounds in oral care products. Specifically, titanium dioxide was found in 68% (n = 111) of the varieties, sodium lauryl sulphate in 67% (n = 108) and paraben in 2% (n = 4), respectively. CONCLUSION: Whilst certain ingredients may raise concerns for potential side effects and health considerations within the human body, the toothpaste has long been regarded as an indispensable tool for maintaining optimal oral and dental health. However, gaining a deeper understanding and conducting research on each constituent that comprises the toothpaste, as well as raising awareness in this regard, holds significant importance for human health.

Patch testing hydroperoxides of limonene and linalool in consecutive patients-Results of the IVDK 2018-2020.

BACKGROUND: Hydroperoxides of limonene (Lim-OOHs) and linalool (Lin-OOHs) are potent contact sensitizers. OBJECTIVES: To investigate the prevalence of positive patch test (PT) reactions to Lim-OOHs and Lin-OOHs in consecutive patients, their demographic factors and concomitant reactions. METHODS: Between 7/2018 and 12/2020, Lim-OOHs 0.3% pet. and Lin-OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim-OOHs and Lin-OOHs. RESULTS: Positive PT results to Lim-OOHs (n = 170, 3.1%) and Lin-OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim-OOHs and Lin-OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides. CONCLUSION: The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended.

Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir™ human airway model in vitro.

The aim of the study was to use multiple in vitro assays to assess the effects of a model irritant, sodium dodecyl sulphate (SDS) (≤10 mM (0.29 %, w/v)), on an in vitro model of the airway, MucilAir™. The use of MucilAir™ in recovery studies was also explored. A 24 h exposure increased IL-8 release at an SDS concentration ≥0.63 mM (0.018 %, w/v). Mucin secretion increased and transepithelial electrical resistance (TEER) decreased at SDS concentrations ≥1.25 mM (0.04 %, w/v). Cytotoxicity (lactate dehydrogenase (LDH) release into basolateral chamber) was observed at SDS concentrations of ≥2.5 mM (0.07 %, w/v). The sensitivity of the assays was IL-8 release > TEER = mucin secretion > LDH release. After 7 days, full or partial recovery was observed for intermediate concentrations of SDS using all assays but not at 5 and 10 mM SDS. Morphologically, erosion and cell loss were observed at these concentrations. Resazurin metabolism at 7 days tended to decrease in a dose-dependent manner at SDS concentrations above 2.5 mM (0.07 %, w/v). Together, these data support a No Observable Effect Level of 0.31 mM (0.009 % w/v) SDS and the use of MucilAir™ as a relevant model for airway toxicity studies.

Comparison of mechanical, chemical and physical human models of in vivo skin damage: Randomized controlled trial.

INTRODUCTION: Human in vivo models of skin damage were often used in research of cutaneous disorders. The most commonly used models were tape-stripping as mechanical, sodium lauryl sulphate-induced irritation as chemical and ultraviolet radiation as physical damage model. In regard to differences between models, they were expected to have different responses to damage and recovery, with unique skin parameters' changes over time. OBJECTIVE: The aim was to compare skin parameters in three different skin damage models on the same anatomical location, with and without topical treatment. METHODS: Four test sites on each forearm were randomly assigned to three skin damage models with the fourth sites on each forearm chosen as a control, undamaged site. Skin parameters were assessed using non-invasive methods. RESULTS: Sodium lauryl sulphate irritation caused the strongest damage with delayed reaction to the irritant. Tape stripping leads to highest initial skin barrier disruption but afterwards it showed the fastest skin recovery. Ultraviolet radiation did not affect skin barrier function, but it elevated skin erythema and melanin level. Tested preparation did not lead to changes in measured parameters. CONCLUSION: The skin of the participants had different response to three skin damage models with distinct changes of skin parameters and recovery. The trial was registered at ClinicalTrials.gov under the identifier NCT03783819.

MALDI mass spectrometry imaging as a complementary analytical method for improved skin distribution analysis of drug molecule and excipients.

In cutaneous drug delivery, it is widely accepted that the choice of excipients affects the delivery of a drug molecule to the skin. MALDI mass spectrometry imaging (MALDI-MSI) is an imaging technique which enables the simultaneous detection of multiple compounds. MALDI-MSI was applied to study the penetration of tofacitinib and excipients in porcine skin from two formulations with sodium lauryl sulphate (SLS) and dexpanthenol (DXP) using Franz diffusion cells. Further, the receptor media was collected for analysis of the permeated amounts of tofacitinib and excipients. The MALDI images showed DXP to be co-localized with tofacitinib in the epidermal and deep dermal region while SLS was distributed in the entire skin compartment. The permeation of tofacitinib for the two formulations was similar after 24 h, whereas, the percentage of permeated DXP was higher than for SLS. This study provided an overview of the skin penetration and permeation of drug molecule and excipients. MALDI-MSI showed differences in the DXP and SLS distribution. This indicates that the excipients interact with the skin through different mechanisms. Compound-specific imaging methods such as MALDI-MSI are potential tools to increase the understanding of the complex interplay between skin, excipients and the drug molecule for optimized cutaneous drug delivery.

Effect of monomer structure of anionic surfactant on voltammetric signals of an anticancer drug: rapid, simple, and sensitive electroanalysis of nilotinib in biological samples.

A rapid, simple, and highly sensitive electroanalytical method was developed for the first time for the detection of ultra-trace amounts of nilotinib in sodium lauryl sulphate media. The electrochemical behavior of nilotinib was investigated on a glassy carbon electrode in the absence and presence of sodium lauryl sulphate media by cyclic voltammetry and adsorptive stripping voltammetric methods. The cyclic voltammograms proved that the electrochemical behavior of nilotinib showed irreversible and diffusion-adsorption-controlled oxidation processes in 0.1 M H2SO4. The effect of surfactant concentration on the first and second peaks of nilotinib was examined. Depending on whether the surfactants had a monomer or monolayer hemimicelle structure, they were attracted to amine moieties at related points in the nilotinib structure through the electrostatic interaction. The sensitivity of the method was markedly enhanced in the presence of surfactants using adsorptive stripping square-wave voltammetry. Under optimum conditions, nilotinib was determined in a concentration range of 2.0 × 10-8 to 2.0 × 10-6 mol L-1, with a limit of detection of 6.33 × 10-9 mol L-1 in 0.1 M H2SO4 containing 2.0 × 10-7 mol L-1 sodium lauryl sulphate. The proposed method can be applied for the sensitive determination of nilotinib in biological samples. Graphical abstract.

The potential of saponin from Jamaica's Blighia sapida (ackee) as a substitute for sodium lauryl sulphate in toothpaste.

Discovering novel means of protection from harmful substances in toothpaste is essential due to its mass production, and frequent exposure to its ingredients by consumers. This method of safeguarding through discovery demonstrates toothpaste safety, which is at risk of being stifled by other commercial priorities. Among the ingredients in toothpaste that cause adverse effects is sodium lauryl sulphate (SLS). An understanding of this source and its effects therefore allows for investigating preventative strategies through the use of safer alternatives. Saponin, a naturally occurring chemical in several plant species was discovered to be an alternative compound that may parallel the effects of sodium lauryl sulphate, yet exude less ill effects. This article highlights the benefits of saponin and its presence in a heavily consumed and exported fruit in Jamaica (ackee, Blighia sapida). The possibility of extracting saponin from ackee, and its use in the toothpaste industry as an alternative to sodium lauryl sulphate are discussed. Through consideration of this alternative, the potential exists to improve the safety of toothpastes and consequently improve oral health.

An Efficient Disinfectant, Composite Material {SLS@[Zn3(CitH)2]} as Ingredient for Development of Sterilized and Non Infectious Contact Lens.

The [Zn3(CitH)2] (1) (CitH4= citric acid), was dispersed in sodium lauryl sulphate (SLS) to form the micelle of SLS@[Zn3(CitH)2] (2). This material 2 was incorporated in hydrogel made by hydroxyethyl-methacrylate (HEMA), an ingredient of contact lenses, toward the formation of pHEMA@(SLS@[Zn3(CitH)2]) (3). Samples of 1 and 2 were characterized by UV-Vis, 1H-NMR, FT-IR, FT-Raman, single crystal X-ray crystallography, X-ray fluorescence analysis, atomic absorption and TG/DTA/DSC. The antibacterial activity of 1-3 as well as of SLS against Gram-positive (Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus)) and Gram-negative (Pseudomonas aeruginosa (PAO1), and Escherichia coli (E. coli)) bacteria was evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and inhibitory zone (IZ). 2 showed 10 to 20-fold higher activity than 1 against the bacteria tested. Moreover the 3 decreases the abundance of Gram-positive microbes up to 30% (St. aureus) and up to 20% (PAO1) the Gram-negative ones. The noteworthy antimicrobial activity of the obtained composite 3 suggests an effective antimicrobial additive for infection-free contact lenses.

In vivo evaluation of fluoride and sodium lauryl sulphate in toothpaste on buccal epithelial cells toxicity.

OBJECTIVES: The present study addresses the effect of fluoride and sodium lauryl sulphate content of toothpaste on oral epithelial cells in vivo conditions. SUBJECTS AND METHOD: Forty volunteers were assigned into two experimental groups, each of them applying the different brand of toothpaste. Every group has been using three different types of toothpaste (non-fluoride and non-SLS, fluoride and non-SLS, and the fluoride and SLS) of the same brand for 6 months, each for 2 months. The buccal epithelial cells were sampled at baseline and 30, 60, 90, 120, 150 and 180 days after the beginning of the research. Effect on DNA damage was analyzed by micronucleus assay Results: After 60 days of use, for both tested kinds of toothpaste with fluoride and without SLS, all studied parameters were not significantly different from the results obtained at the time when the participants used a non-fluoride toothpaste. While, after 60 days of use, for one kind of toothpaste with SLS and fluoride, was observed significantly higher incidence of pyknotic cells (2.20 ± 0.95, 0.00 ± 0.00 vs. 0.05 ± 0.22, respectively; p = .001), cells with karyorrhexis (2.35 ± 1.14, 0.85 ± 0.93 vs. 0.40 ± 0.68, respectively; p = .001), and nuclear buds (1.35 ± 0.68, 0.45 ± 0.51 vs. 0.45 ± 0.60, respectively; p = .001), compared to toothpastes of the same brand with fluoride and without SLS, and without fluoride and without SLS, for the same period. CONCLUSIONS: Based on the results, can be concluded that there is no fluorine-dependent cytotoxic or genotoxic effect, while SLS dentifrice increases the number of nuclear morphological changes in buccal epithelial cells.

Validation of an optimised protocol for quantification of microplastics in heterogenous samples: A case study using green turtle chyme.

Quantifying the extent of microplastic (<5 mm) contamination in the marine environment is an emerging field of study. Reliable extraction of microplastics from the gastro-intestinal content of marine organisms is crucial to evaluate microplastic contamination in marine fauna. Extraction protocols and variations thereof have been reported, however, these have mostly focussed on relatively homogenous samples (i.e. water, sediment, etc.). Here, we present a microplastic extraction protocol for examining green turtle (Chelonia mydas) chyme (i.e. ingested material and digestive tract fluid), which is a heterogeneous composite of various organic dietary items (e.g. seagrass, jellyfish) and incidentally-ingested inorganic materials (sediment). Established extraction methods were modified and combined. This protocol consists of acid digestion of organic matter, emulsification of residual fat, density separation from sediment, and chemical identification by Fourier transform-infrared spectroscopy. This protocol enables the extraction of the most common microplastic contaminants>100 µm: polyethylene, high-density polyethylene, (aminoethyl) polystyrene, polypropylene, and polyvinyl chloride, with 100% efficiency. This validated protocol will enable researchers worldwide to quantify microplastic contamination in turtles in a reliable and comparable way. •Optimization of microplastic extraction from multifarious tissues by applying established methods in a sequential manner.•Effective for heterogenous samples comprising organic and inorganic material.

Pulmonary delivery of liposomal dry powder inhaler formulation for effective treatment of idiopathic pulmonary fibrosis.

Dry powder inhaler Liposomes were prepared to investigate the effectiveness of pulmonary delivery of Colchicine and Budesonide for Idiopathic Pulmonary fibrosis. Budesonide (BUD) and Colchicine (COL) liposomes were prepared by thin layer film hydration method (TFH) using 1,2-Dipalmitoyl-sn-glycero-3- phosphoglycerol sodium (DPPG), Hydrogenated Soyaphosphotidylcholine (HSPC), Soyaphosphatidylcholine (SPC), cholesterol (CHOL) and drug in different weight ratios. The optimum lipid composition for BUD (74.22 ± 0.97%) was DPPG: HSPC: CHOL (4:5:1) and for COL (50.94 ± 2.04%) was DPPG: SPC: CHOL (3:6:1). These compositions retained drug for a longer period of time so selected for further study. Liposomes were found to be spherical in shape with mean size below 100 nm. Liposomes lyophilized using Mannitol as carrier and cryoprotectant showed high entrapment efficiency (97.89 - 98.6%). The powder was dispersed through an Andersen cascade impactor to evaluate the performance of the aerosolized powder. It was found that prepared liposomal dry powder inhaler (DPIs) sustained the drug release up to 24 hours. Optimized Budesonide DPI Formulation B2 (86.53 ± 1.9%), Colchicine DPI Formulation C2 (90.54 ± 2.3 %) and BUD and COL DPI Combination M2 (89.91 ± 1.8%, 91.23 ± 1.9%). Histopathological results, measurements of lung hydroxyproline content, Myeloperoxidase activity indicated that liposomal dry powder inhaler administration attenuates lung fibrosis induced by bleomycin. Long term stability studies indicated that lyophilised BUD and COL liposomes were stable for 6 months at (25 °C ± 2 °C, 60% ± 5% RH) and refrigerated conditions (2 - 8 °C). These results supported that combination of budesonide and colchicine liposomal dry powder inhaler pulmonary drug delivery for treatment of idiopathic Pulmonary Fibrosis exhibits prolonged drug retention at targeted site and reduces the systemic exposure.

Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying.

Hypromellose acetate succinate (HPMCAS) microparticles containing the poorly-water soluble drug celecoxib (CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.

The effectiveness of a dentifrice without sodium lauryl sulphate on dental plaque and gingivitis - a randomized controlled clinical trial.

OBJECTIVES: The purpose of the study was to evaluate the effect on dental plaque and gingivitis of a dentifrice without sodium lauryl sulphate (SLS) compared to two SLS-containing dentifrices. MATERIAL AND METHODS: For this double-blind, parallel study, 90 volunteers having moderate gingival inflammation (≥40%) were randomly divided among three groups: one group using non-SLS dentifrice containing enzymes, colostrum and low concentrations of zinc and two control groups each using different SLS-containing dentifrices. Dental plaque scores (Turesky modification of Quigley & Hein) and gingivitis scores (Bleeding On Marginal Probing) were assessed at baseline, after 2 and 4 weeks. RESULTS: Eighty-nine participants provided evaluable data. A slight decrease in gingivitis scores was observed for all groups over 4 weeks, which was statistically significant for the non-SLS group. Mean values for dental plaque scores did not show major differences over 4 weeks. For both parameters, no significant differences between groups could be observed at any time point. Patient appreciation was in favour of the SLS groups especially regarding the foaming effect. CONCLUSION: No significant differences could be observed with respect to the effect on plaque and gingivitis between SLS-containing and SLS-free dentifrice containing enzymes, colostrum and low concentration zinc. Patients enjoyed the duration of taste and the 'foaming effect' of SLS-containing dentifrices better.

Chlorhexidine mouthwash and sodium lauryl sulphate dentifrice: do they mix effectively or interfere?

FOCUSED QUESTION: What is the effectiveness of a chlorhexidine (CHX) mouthwash used in combination with a sodium lauryl sulphate (SLS) dentifrice on the parameters of plaque and gingivitis? MATERIAL AND METHODS: MEDLINE-PubMed, Cochrane-CENTRAL, EMBASE and other electronic databases were searched up to July 2014. The inclusion criteria were (randomized) controlled clinical trials, subjects ≥18 years of age with good general health. Papers evaluating the effect of CHX mouthwash used in combination with SLS dentifrice or a dentifrice slurry compared with CHX mouthwash as a single oral hygiene intervention or in combination with an SLS-free dentifrice were included. From the eligible studies, data were extracted, and a meta-analysis was performed when feasible. RESULTS: Independent screening of 83 unique papers resulted in four eligible publications, with nine comparisons. The meta-analysis showed that when an SLS dentifrice was used as a slurry rinse, the interference on the plaque-inhibiting effect of a CHX mouthwash was significantly decreased (MD 0.33; P ≤ 0.00001; 95% CI: <0.24; 0.42>). No significant difference was observed when SLS dentifrice was applied as a paste in combination with CHX mouthwash (MD 0.08; P = 0.42; 95% CI: <-0.26; 0.11>). Descriptive and subgroup analyses support these findings. Moreover, the observed effect for the dentifrice paste occurred regardless of the order of use. CONCLUSION: This review demonstrates that when CHX mouthwash is recommended, it can be used in combination with an SLS dentifrice without any interference regarding its inhibiting effect on dental plaque, regardless of the order of use. Consequently, the collective evidence indicates that the combined use of dentifrice and CHX mouthwash is not contraindicated. However, this recommendation has been graded as moderate taking into account a potential publication bias because three of the four included studies emerged from the same research group.

Design and development and evaluation of candesartan cilexetil liquid filling formulations.

Most of the currently available drugs are having poor water solubility and suffer from low oral bioavailability. One of the most promising approaches to deliver such insoluble drugs is by dissolving it in lipids, liquids or semi-solids to formulate new products.[1] Candesartan meets the requirement of high potency but it is poorly absorbed when administered as tablets. Therefore the prodrug Candesartan cilexitil is developed.[2] Two piece hard gelatin liquid filling capsules are one of the most logical approaches when choosing the best dosage form to deliver these new liquid formulations.[1] Liquid filled formulations were prepared by employing different cosolvents and surfactants. The formulation containing SLS-2%, PVP- 17.5%, PEG-15%, and PG-53% exhibited desire solubility, rheological property and found to be stable in hard gelatin capsules.

Optimization of long circulating mixed polymeric micelles containing vinpocetine using simple lattice mixture design, in vitro and in vivo characterization.

The aim of this study was to increase the in vivo mean residence time of vinpocetine after IV injection utilizing long circulating mixed micellar systems. Mixed micelles were prepared using Pluronics L121, P123 and F127. The systems were characterized by testing their entrapment efficiency, particle size, polydispersity index, zeta potential, transmission electron microscopy and in vitro drug release. Simple lattice mixture design was planned for the optimization using Design-Expert(®) software. The optimized formula was lyophilized, sterilized and imaged by scanning electron microscope. Moreover, the in vivo behavior of the optimized formula was evaluated after IV injection in rabbits. The optimized formula, containing 68% w/w Pluronic L121 and 32% w/w Pluronic F127, had the highest desirability value (0.621). Entrapment efficiency, particle size, polydispersity index and zeta potential of the optimized formula were 50.74 ± 3.26%, 161.50 ± 7.39 nm, 0.21 ± 0.03 and -22.42 ± 1.72 mV, respectively. Lyophilization and sterilization did not affect the characteristics of the optimized formula. Upon in vivo investigation in rabbits, the optimized formula showed a significantly higher elimination half-life and mean residence time than the market product. Finally, mixed micelles could be considered as a promising long circulating nanocarrier for lipophilic drugs.

Characterizing the immunological effects of oral healthcare ingredients using an in vitro reconstructed human epithelial model.

Oral healthcare products are well tolerated and while adverse occurrences are rare there is still a need to explore the interaction between these products and the oral mucosa. This study assessed the effects of oral healthcare ingredients: sodium lauryl sulphate (SLS), a detergent; cinnamic aldehyde (CA), a flavouring agent; and cetylpyridinium chloride (CPC), an antiseptic, using a reconstructed human oral mucosal model (OMM). Differential release of inflammatory cytokines IL-1α, IL-8 and cytotoxicity was compared with other known irritants and sensitizers to identify a signature response profile that could be associated with oral mucosal irritation. Response profiles differed with irritants being more cytotoxic. CA and control sensitizers nickel sulphate (NiSO4) and 1-chloro-2,4-dinitrochlorobenzene (DNCB) released lower levels of IL-1α than CPC and control irritant benzalkonium chloride (BC), whereas the opposite was observed for IL-8. Significant levels of IL-8 and IL-1α were released with 5-15 mg/ml (0.5-1.5% w/v) SLS. Quantitative PCR indicated that cytokine release at lower SLS concentrations is not entirely due to cell necrosis but in part due to de novo synthesis. These findings suggest that the OMM can be used to predict oral irritation thus making it a potentially valuable model for screening new oral healthcare ingredients prior to clinical release.

Comparison of in vitro toxicity of mainstream cigarette smoke particulate matter from nano- to micro-size.

In order to investigate the interrelationship between particulate matter (PM) size and in vitro toxicological effects of mainstream cigarette smoke, PM sized between 10 nm and 10 µm in mainstream cigarette smoke was sampled and divided into six stages. The in vitro cytotoxicity, genotoxicity and cell inhibition effects of PM were assessed by the neutral red cytotoxicity assay, Salmonella mutagenicity assay, micronucleus test and flow cytometry analysis, respectively. The results showed that all test samples were cytotoxic in the neutral red cytotoxicity assay. The IC50 values in the small-sized groups were significantly lower than those in the large-sized groups. Most test samples were mutagenic in the Salmonella mutagenicity assay (TA98 with S9 and TA100 with S9) and increased the frequency of micronucleated cells. Most PM disturbed the normal progression of the cell cycle, resulting in the accumulation of cells in the G0/G1 phase and the induction of apoptosis. In these tests, PM of a large size induced less toxicity compared with PM of a small size. These findings suggest that most PM samples induced toxicity in vitro, and PM of a small size was more toxic than PM of a large size.

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05) in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (p<0,05) na taxa de dissolução foram registradas com a mudança na concentração de LSS em diferentes meios de dissolução. A formulação T3 contendo LSS a 1% foi considerada a melhor formulação otimizada com base nos ensaios de desintegração, dissolução e fatores de semelhança e dissimilaridade.

Improving the de-agglomeration and dissolution of a poorly water soluble drug by decreasing the agglomerate strength of the cohesive powder.

Influence of ternary, poorly water-soluble components on the agglomerate strength of cohesive indomethacin mixtures during dissolution was studied to explore the relationship between agglomerate strength and extent of de-agglomeration and dissolution of indomethacin (Ind). Dissolution profiles of Ind from 20% Ind-lactose binary mixtures, and ternary mixtures containing additional dibasic calcium phosphate (1% or 10%; DCP), calcium sulphate (10%) and talc (10%) were determined. Agglomerate strength distributions were estimated by Monte Carlo simulation of particle size, work of cohesion and packing fraction distributions. The agglomerate strength of Ind decreased from 1.19 MPa for the binary Ind mixture to 0.84 MPa for 1DCP:20Ind mixture and to 0.42 MPa for 1DCP:2Ind mixture. Both extent of de-agglomeration, demonstrated by the concentration of the dispersed indomethacin distribution, and extent of dispersion, demonstrated by the particle size of the dispersed indomethacin, were in descending order of 1DCP:2Ind>1DCP:20Ind>binary Ind. The addition of calcium sulphate dihydrate and talc also reduced the agglomerate strength and improved de-agglomeration and dispersion of indomethacin. While not definitively causal, the improved de-agglomeration and dispersion of a poorly water soluble drug by poorly water soluble components was related to the agglomerate strength of the cohesive matrix during dissolution.