Drug content determination of low-dosed hot-melt extruded filaments using Raman spectroscopy.

The aim of this study was to evaluate the suitability of a non-disruptive Raman spectroscopic method to quantify drug concentrations below 5 w% within a polymer matrix produced by hot-melt extrusion (HME). For calibration, praziquantel (PZQ)-polyvinylpyrrolidone-vinylacetat-copolymer (PVP-VA) mixtures were extruded. By focusing the laser light of the Raman probe to a diameter of 1 mm and implementing a self-constructed filament holder, the signal-to-noise (S/N) ratio could be reduced considerably. The obtained Raman spectra show quite high fluorescence, which is likely to be caused by dissolved pharmaceutical active ingredient (API) in the polymer matrix. For content determination, HPLC analysis was conducted as a reference method using the same filament segments. A partial least squares (PLS) model, regressing the PZQ concentrations from HPLC method analysis versus the off-line collected Raman spectra, was developed. The linear correlation for a suitable extrusion run for the production of low-dosed filaments (extrusion 1, two kneading zones) is acceptable (R2 = 0.9915) while the correlation for a extrusion set-up with low miscibility (extrusion 2; without kneading zone) is unacceptable (R2 = 0.5349). The predictive performance of the calibration model from extrusion 1 is rated by the root mean square error of estimation (RMSEE), which was 0.08%. This calibration can now be used to validate the content of low-dosed filaments during HME.

Mechanistic insights into the effect of drug content on adhesive properties of transdermal patch containing lidocaine.

This study aims to shed light on the relationship between drug content and adhesive properties in drug-in-adhesive transdermal patch, and to elucidate molecular mechanisms from the perspective of polymer chain mobility. Lidocaine was selected as model drug. Two acrylate pressure sensitive adhesives (PSAs) with different polymer chain mobility were synthesized. Tack adhesion, shear adhesion and peel adhesion of PSAs with 0, 5%, 10%, 15% and 20% w/w lidocaine contents were tested. Polymer chain mobility was determined by rheology and modulated differential scanning calorimetry experiments. Drug-PSA interaction was analyzed by FT-IR. The effect of drug content on free volume of PSA were determined by positron annihilation lifetime spectroscopy and molecular dynamics simulation. It was found that the polymer chain mobility of PSA was increased with increasing drug content. Due to the variation of polymer chain mobility, tack adhesion increased, and shear adhesion decreased. It was proved that interactions between polymer chains were destroyed by drug-PSA interactions, free volume between polymer chains was expanded, resulting in the increase of polymer chain mobility. We can conclude that the effect of drug content on polymer chain mobility should be considered, when designing a transdermal drug delivery system with controlled and satisfactory adhesion.

Evaluation of solubility, photostability and antioxidant activity of ellagic acid cyclodextrin nanosponges fabricated by melt method and microwave-assisted synthesis.

Ellagic acid (EA) is a polyphenolic bioactive with a wide range of pharmacological activities. Regrettably, it possesses poor solubility, stability and permeability (in the gastrointestinal tract); and first-pass metabolism. Therefore, to address these challenges, the present research was aimed to encapsulate EA in cyclodextrin nanosponges (CDNS). Herein, the melt method and microwave-assisted technique have been employed for crafting CDNS. EA was loaded in CDNS via freeze-drying, followed by appropriate characterization. EA-CDNS were also assessed for encapsulation, particle size, zeta potential, and polydispersity index, which presented satisfactory results. In vitro, antioxidant activity was conducted using the DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. The solubilization efficacy of EA was analyzed in distilled water and compared with CDNS, which demonstrated ten folds augmentation for the selected batch. A remarkable improvement in the photostability of EA was also observed after its inclusion. In nutshell, the results demonstrated the superiority of the melt method in terms of solubility, entrapment, photostability, and antioxidant potential.

Drug Content Uniformity: Quantifying Loratadine in Tablets Using a Created Raman Excipient Spectrum.

Raman spectroscopy has proven valuable for determining the composition of manufactured drug products, as well as identifying counterfeit drugs. Here we present a simple method to determine the active pharmaceutical ingredient (API) mass percent in a sample that does not require knowledge of the identities or relative mass percents of the inactive pharmaceutical ingredients (excipients). And further, we demonstrated the ability of the method to pass or fail a manufactured drug product batch based on a calculated acceptance value in accordance with the US Pharmacopeia method for content uniformity. The method was developed by fitting the Raman spectra of 30 Claritin® tablets with weighted percentages of the Raman spectrum of its API, loratadine, and a composite spectrum of the known excipients. The mean loratadine mass of 9.79 ± 40 mg per 100 mg tablet compared favorably to the 10.21 ± 0.63 mg per 100 mg tablet determined using high-performance liquid chromatography, both of which met the acceptance value to pass the 10 mg API product as labelled. The method was then applied to a generic version of the Claritin product that employed different excipients of unknown mass percents. A Raman spectrum representative of all excipients was created by subtracting the API Raman spectrum from the product spectrum. The Raman spectra of the 30 generic tablets were then fit with weighted percents of the pure loratadine spectrum and the created excipient spectrum, and used to determine a mean API mass for the tablets of 10.12 ± 40 mg, again meeting the acceptance value for the 10 mg API product. The data suggest that this simple method could be used to pass or fail manufactured drug product batches in accordance with the US Pharmacopeia method for content uniformity, without knowledge of the excipients.

Development and uniformity evaluation of low-dose medicated chewing gums prepared by compression method.

The aim of this work was to develop medicated chewing gums (MCGs) containing 10 mg of lysozyme hydrochloride (LH) and 20 mg of ascorbic acid (AsA) obtained by the compression method with Health in Gum® (HiG®) PWD 01 as a compressible gum base. Because of a low content of active ingredients, it was essential to choose the way of adding them to the tableting mass and evaluate their distribution homogeneity in the dosage units. The blends for compression were prepared by two methods: the first one was simple mixing of all components; the second one included the step of wet granulation of a three-component mixture - LH, sucralose and a taste additive. Flow properties of LH, AsA, HiG®, LH granules and blends for compression were studied. MCGs were evaluated according to Ph.Eur. 9.0 Chapters 2.9.5, 2.9.6 and 2.9.40. AsA and HiG® were characterized as free flowing, while LH had insufficient flow properties. Compared with a simple mixed blend, the granulation step allowed significantly improving flow properties of the final blend for compression. Unlike MCGs compressed from the simple mixed blend, MCGs prepared through the granulation step met Ph.Eur. 9.0 Chapter 2.9.40 requirements. The propriety of MCG preparation method involving the step of wet granulation also has been confirmed by mass and drug content uniformity tests.

Digital UV/VIS imaging: A rapid PAT tool for crushing strength, drug content and particle size distribution determination in tablets.

The Process Analytical Technology (PAT) and the Quality-by-Design (QbD) approaches can efficiently facilitate the shift to the desired continuous manufacturing and real time release testing (RTRT). By this, it is vital to develop new, in-line analytical methods which fulfil the pharmaceutical requirements. The fast-developing digital imaging-based machine vision systems can provide revolutionary solutions not just in the automotive industry but in the pharmaceutical technology, as well. This study aimed to explore the capabilities of UV/VIS-based machine vision in tablet inspection as a PAT tool for the determination of compression force and crushing strength, drug content and drug distribution in tablets using meloxicam a yellow model drug. In the case of determining the compression force and crushing strength, the application of multivariate wavelet texture analysis (MWTA) based models provided relatively low prediction errors. To predict the drug content of meloxicam tablets CIELAB or RGB colorspace based algorithms were successfully developed and validated. UV/VIS imaging was also used to map the particle size distribution and spatial distribution of meloxicam, the results were compared to chemical maps obtained by Raman microscopy. Digital imaging combined with multivariate data analysis might be a valuable, high throughput, in-line PAT tool for automated inspection of pharmaceutical tablets.

Exploring the influence of drug content on DPI powder properties and potential prediction of pulmonary drug deposition.

Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.

Controlled release of resveratrol and xanthohumol via coaxial electrospinning fibers.

Synergistic delivery of two drugs is a desirable choice to overcome drug resistance. Resveratrol (RES) and xanthohumol (XAN) which are both new drugs originated from plants exhibit great potential in the treatment of cancer, but there are few studies on combining them in a delivery system. In this work, a new core/shell fiber mesh containing RES and XAN was designed out via coaxial electrospinning, and the effect of drug content on the medicated fibers was discovered. RES/polyethylene oxide (PEO) could be well combined with XAN/Poly(lactide-glycolide) (PLGA) to make core/shell fibers, but fibrous morphology worsened with increasing drug content of the core or shell to some extent. The core/shell was amorphous nature, and changing drug content had little influence on the wetability of the core/shell fibers. The release accelerated with drug content increasing in the fibers, and RES and XAN showed gradient release, which the release rate of RES was slower than XAN. These two drugs could sustain release for 350 h. When the blend ratios of RES/PEO and XAN/PLGA were 50/50 and 10/90 in the fibers, the fiber mesh showed the best mechanical properties, of which the tensile strength and elongation at break were 2.85 ± 0.10 MPa and 55.23 ± 2.53%, respectively. The medicated fibers presented good characteristics of inhibiting breast cancer cell activity.

High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling.

PURPOSE: This study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular dosage form design concepts. METHODS: FDM was used to generate ~0.5 mm thick discs of varying diameter (2-10 mm) from melt-extruded feedstocks based on 10% to 50% w/w felodipine in ethyl cellulose. Drug content was determined by UV spectroscopy and dispensing precision from printed disc mass. RESULTS: Mean felodipine content was within ±5% of target values for all print volumes and compositions including contents as high as ~50% w/w. However, poor dispensing precision was evident at all print volumes. CONCLUSIONS: In pursuit of dose flexibility, this successful demonstration of dose window extension using high content solid dispersions preserves FDM design flexibility by maintaining applicability to drugs of varying potencies. The achieved uniformity of content supports the application of varying content solid dispersions to modular dosage form concepts to enhance dose flexibility. However, poor dispensing precision impedes its utilisation until appropriate compatibility between FDM hardware and materials at varying drug contents can be attained.

A QCM-based assay of drug content in Eudragit RS 100-based delivery systems.

A specific version of the quartz crystal microbalance method has been proposed for quantitative evaluation of drug content in polymeric drug carrier systems. In this study, ammonio methacrylate copolymer (type B) microparticles and their standard solutions have been prepared and loaded with set amounts of the medications diltiazem (base) and lidocaine. The analytes have been segregatim deposited on the surface of the resonator and the drug content in them has been derived from the downshift of the resonance frequency produced by irreversible interaction of the drug molecules with irradiating hydrochloric gas. The obtained results have been statistically processed on a number of samples and have been found to exhibit excellent coherence to set theoretical values. As an alternative, the conventional pharmacopoeial UV-Vis spectral method has also been separately applied to studied samples, revealing worsened performance in the case of lidocaine due to polymer matrix interference. Thus the universality of the QCM method has been proved to add to its versatility and precision. The method appears to be readily applicable to the routine pharmaceutical quantity control of bulk and multiparticulate drug forms.

Evaluation of the suitability of a fluidized bed process for the coating of drug-eluting stents.

Drug-eluting stents are often coated using single-stent coating techniques. In pharmaceutical industry, single-tablet coating is unthinkable. Instead large batches of tablets are coated in fluidized bed apparatuses or pan coaters. Therefore, it was the aim of this work to evaluate whether stents can be coated using a fluidized bed process. For this purpose stents were coated with the model fluorescent drug triamterene embedded in ammonium methacrylate copolymer. Different stent lengths as well as different coating yields were assessed and also a drug-free topcoat was evaluated. The coated stents were analysed regarded coating layer mass, drug content, surface structure, coating thickness and drug release. Furthermore, coating yield and stent defect rate were examined. Except for one stent configuration good results were obtained without optimization of process parameters which indicates the suitability of the method to coat large amounts of stents simultaneously in principle. Drug release was tuneable over a wide range of time spans and a wide range of drug loadings was produced. Further work will be necessary to transform the results of this study from a model stent to a clinically relevant product.

Utility of Microcrystalline Cellulose for Improving Drug Content Uniformity in Tablet Manufacturing Using Direct Powder Compression.

Direct powder compression is the simplest tablet manufacturing method. However, segregation occurs when the drug content is low. It is difficult to assure drug content uniformity in these cases. In this study, we evaluated microcrystalline cellulose (MCC) as a segregation inhibitor in pharmaceutical powders. We assessed the influence of MCC concentration and mixing time on the physical properties of tablets. The tablet formulation comprised acetaminophen, lactose hydrate, cornstarch, MCC (0%, 10%, or 20%), croscarmellose sodium, and magnesium stearate (Mg-St). All powders except Mg-St were premixed for 5, 15, or 25 min. Mg-St was then added and mixed for 5 min to prepare nine pharmaceutical powders. Flowability index and practical angle of internal friction were measured. Tablets were also prepared, and their weight variation, hardness, friability, disintegration time, and drug content variation were evaluated. MCC slightly decreased pharmaceutical powder flowability. Tablet hardness increased and disintegration time decreased with increasing MCC concentration. MCC mixed for ≥ 15 min also significantly lowered drug content variation. A contour plot was prepared to assess the effect of MCC concentration and mixing time on the physical properties of tablets. It was determined that tablets with 50-80 N hardness, ≤ 3.5 min disintegration time, and ≤ 3% drug content variation can be prepared when MCC concentration is 6.5-8.5% and the mixing time is 19-24 min. Therefore, MCC is effective as a segregation inhibitor, and the addition of MCC to tablet formulation improves drug content uniformity.

Investigation of Absorption Routes of Meloxicam and Its Salt Form from Intranasal Delivery Systems.

The aim of this article was to study the trans-epithelial absorption to reach the blood and to target the brain by axonal transport using nasal formulations with nanonized meloxicam (nano MEL spray) and its salt form known as meloxicam potassium monohydrate (MELP spray). The physicochemical properties and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out. These forms were first investigated in "nose-to-brain" relation. It was found that the in vitro study and in vivo study did not show any significant correlation. In vitro experiments demonstrated faster dissolution rate and higher diffusion of MELP from the spray compared with the nano MEL spray. The administration of the nano MEL spray resulted in faster absorption and constant plasma concentration of the drug after five minutes of administration as compared to MELP. The axonal transport of the drug was justified. MEL appeared in the brain tissues after the first five minutes of administration in the case of both spray forms, but its amount was too small in comparison with the total plasma concentration. The application of the nano MEL spray resulted in the same AUC in the brain as the intravenous injection. The "nose-to-blood" results predicted the nasal applicability of MEL and MELP in pain management. The "nose-to-brain" pathway requires further study.

Development of a novel pelletization technique through an extremely high-shear process using a mechanical powder processor to produce high-dose small core granules suitable for film coating.

We established an extremely high-shear melt pelletization technique using a mechanical powder processor to produce high-dose granules smaller than 300 µm with properties suitable for film coating. A mixture of ethenzamide and polyethylene glycol (used as a low-melting binder) at various weight ratios was mechanically treated under various jacket temperatures. When the jacket temperature was set to 50 °C or greater, the product temperature reached the melting point of the binder, resulting in pelletization. The drug powder were pelletized with a small amount of binder to yield pellets of approximately 150 µm with a drug content of more than 90%. The mechanism of melt pelletization through ultrahigh shearing involves a series of nucleation, consolidation, coalescence and breakage stages. The power consumption profile corresponding to each stage in the pelletization revealed that pellets between 75 and 300 µm were effectively obtained at a large power consumption peak. The resultant pellets showed comparative sphericity and smoothness, and higher durability than commercial core granules for film coating. In conclusion, this study demonstrates that the extremely high-shear melt pelletization technique can give drug pellets with desirable properties as core particles for the coating process.

Non-destructive prediction of the drug content of an acetaminophen suppository by near-infrared spectroscopy and X-ray computed tomography.

The purpose of this study is to develop non-destructive methods to determine the drug content of suppositories using near-infrared (NIR) spectrometry and X-ray computed tomography (XCT). The suppository samples (acetaminophen content: 0, 100, 200, 300, 400 and 500 mg/suppository) consisted of acetaminophen powder and hard fat. NIR spectra of 18 standard suppository samples were recorded, and the data were divided into two wave number ranges, 4000-10 000 cm(-1) (LR), and 4280-6650 cm(-1) (SR). The best calibration model was determined to minimize the standard error of cross-validation (SECV) by the leave-one-out method in the partial least squares regression (PLS). Sliced XCT images of the suppositories were measured, and apparent density (AD) was evaluated using the image of the sample. The NIR models gave the best correlation coefficient constant (R) values, since the results for LR and SR gave straight lines with R of 0.9274 and 0.9707, respectively. The AD of the suppositories by XCT increased with increasing drug content, and the relationship between the AD and drug content had a straight line with R of 0.9958. Both NIR and X-ray CT performed accurate measurements of suppository samples through plastic packaging.

Accuracy of tablet splitting: Comparison study between hand splitting and tablet cutter.

BACKGROUND: Tablet splitting is often used in pharmacy practice to adjust the administered doses. It is also used as a method of reducing medication costs. OBJECTIVE: To investigate the accuracy of tablet splitting by comparing hand splitting vs. a tablet cutter for a low dose drug tablet. METHODS: Salbutamol tablets (4 mg) were chosen as low dose tablets. A randomly selected equal number of tablets were split by hand and a tablet cutter, and the remaining tablets were kept whole. Weight variation and drug content were analysed for salbutamol in 0.1 N HCl using a validated spectrophotometric method. The percentages by which each whole tablet's or half-tablet's drug content and weight difference from sample mean values were compared with USP specification ranges for drug content. The %RSD was also calculated in order to determine whether the drugs met USP specification for %RSD. The tablets and half tablets were scanned using electron microscopy to show any visual differences arising from splitting. RESULTS: 27.5% of samples differed from sample mean values by a percentage that fell outside of USP specification for weight, of which 15% from the tablet cutter and 25% from those split by hand fell outside the specifications. All whole tablets and half tablets met the USP specifications for drug content but the variation of content between the two halves reached 21.3% of total content in case of hand splitting, and 7.13% only for the tablet cutter. The %RSDs for drug content and weight met the USP specification for whole salbutamol tablets and the half tablets which were split by tablet cutter. The halves which were split by hand fell outside the specification for %RSD (drug content = 6.43%, weight = 8.33%). The differences were visually clear in the electron microscope scans. CONCLUSION: Drug content variation in half-tablets appeared to be attributable to weight variation occurring during the splitting process. This could have serious clinical consequences for medications with a narrow therapeutic-toxic range. On the basis of our results, we recommend to avoid tablet splitting whenever possible or the use of an accurate tablet splitting device when splitting cannot be avoided.

Estimation of content of anti-TB drugs supplied at centres of the Revised National TB Control Programme in Tamil Nadu, India.

OBJECTIVE: To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India. METHODS: Eight districts across the state were selected, and the following drugs were collected from five settings (District TB centre, TB unit, designated microscopy centres, DOT providers) in each district: rifampicin (150 and 450 mg), isoniazid (300 mg), pyrazinamide (500 and 750 mg), ethambutol (400 and 600 mg), ethionamide (250 mg), levofloxacin (500 mg) and cycloserine (250 mg). A maximum of 10 tablets/capsules were collected from each setting. The drugs were coded prior to analysis. All drugs were assayed by validated spectrophotometric methods. The acceptable limits for drug content were taken as 90-110% of the stated content. RESULTS: More than 90% of tablets of rifampicin 450 mg, isoniazid 300 mg, pyrazinamide 500 and 750 mg, ethambutol 400 and 600 mg and ethionamide 250 mg were within acceptable limits. Eighty per cent of rifampicin 150 mg, 21% of cycloserine 250 mg and 87% of levofloxacin 500 mg were within acceptable limits. The mean cycloserine content was below the acceptable limit in all districts, the mean drug content being 200 mg (range: 108-245 mg). CONCLUSION: This systematic study showed that the stated drug content of cycloserine was not reached in all districts. Deterioration of cycloserine could be minimised by storing the drug in refrigerators. The geographical location of the districts had no influence on the drug content.

Development and characterization of pharmacokinetic parameters of fast-dissolving films containing levocetirizine.

A fast-dissolving film containing levocetirizine, a non-sedative antihistamine drug, was developed using pullulan, xanthan gum, propylene glycol, and tween 80 as the base materials. The drug content of the prepared films was within an acceptable limit as prescribed by the USP. The film exhibited excellent stability for four months when stored at 40 °C and 75% humidity. In vitro dissolution studies suggested a rapid disintegration, in which most of levocetirizine (93.54 ± 3.9%) dissolved within 90 seconds after insertion into the medium. Subsequently, Sprague-Dawley rats were used to compare the pharmacokinetic properties of the film preparation administered to the oral cavity, to those with oral administration of the pure drug solution. The pharmacokinetic parameters were similar between the two groups in which AUC(0-t) (ng h/ml), AUC(0-∞) (ng h/ml) C(max) (ng/ml), T(max) (min), K(el) (h(-1)), and t(1/2) (h) of the reference were 452.033 ± 43.68, 465.78 ± 48.16, 237.16 ± 19.87, 30, 0.453 ± 0.051, and 1.536 ± 0.118, respectively, for the film formulation 447.233 ± 46.24, 458.22 ± 46.74, 233.32 ± 17.19, 30, 0.464 ± 0.060, and 1.496 ± 0.293, respectively. These results suggest that the present levocetirizine containing fast-dissolving film is likely to become one of the choices to treat different allergic conditions.

Preparation of naproxen microemulsion-gel with high drug content and investigation of its in vitro transdermal delivery ability / 中国药学杂志

OBJECTIVE: To prepare naproxen microemulsion-gel with high drug content and adhesiveness, and investigate its in vitro transdermal delivery ability. METHODS: The ranges of microemulsion with the mixture of Tween 80 and Tween 20 as surfactant, carbitol as cosurfactant, peponida as oil, were defined through construction of the pseudo-ternary phase diagrams. Drug-loaded microemulsions were prepared by phase transfer temperature method. Naproxen microemulsion-gel was prepared by directly adding carbomer 980 into its microemulsion. The diffusion studies of all formulations were performed using a drug diffusion apparatus. The mean droplet sizes of naproxen microemulsion were measured via dynamic light scattering(DLS) on a Zetasizer, their microstructures were observed by transmission electron microscope(TEM). RESULTS: Microemulsion range was largest when the mass ratio of Tween 80 and Tween 20 was 3:1, surfactant and cosurfactant was 2:1. While the microemulsion composed of 5% peponida, 35% emulsifier and 60% water, drug loaded in microemulsion can attain 4%, which was accorded with the characterization of microemulsion. Adding 2.5% carbomer 980 into optimization microemulsion, even and transparence microemulsion-gel was obtained, which has the combination of o/w microstructure of microemulsion and the three-dimensional gel network of hydrogel. The viscosity of microemulsion-gel was increased from 104.5 mPa · s to 18.9 Pa · s, the steady-state permeation rates through excised cavia skin increased from(531.912±1.3) to(640.327±0.7) μg · cm-2 · h-1. CONCLUSION Naproxen microemulsion-gels prepared by selected carbitol as cosurfactant can obtain high drug content and percutaneous absorbtion, exhibit favourable adhesiveness, which may be a promising new dosage form for transdermal delivery of naproxen.

Monitorization of drug content in furosemide and lorazepam tablets stored in multidose pill boxes.

BACKGROUND: Therapeutic nonadherence is a major health problem, particularly when therapeutic regimens are complex and long-lasting. Therefore, tools such as multidose pill boxes have been designed to provide the means for higher therapeutic compliance. However, no studies are available reporting on their capacity to keep the drug content of the stored tablets unaltered. OBJECTIVE: This work aimed at monitoring the drug content of tablets stored in multidose boxes for a period of two weeks. MATERIALS AND METHODS: Furosemide and lorazepam were selected as model drugs, given their frequent chronic use, which is coherent with the profile of medicines susceptible of storage in the referred boxes. Variations of the tablets drug content were assessed as a function of temperature (25°C and 40°C) and the presence of blister. RESULTS AND DISCUSSION: The obtained results allowed concluding that concerning temperature, only lorazepam tablets registered drug content alterations and only when stored at 40°C. On the other side, it was concluded that the absence of blister does not compromise the drug content of the studied tablets. CONCLUSION: In the specific conditions of this study, the storage of these medicines in multidose boxes is considered reliable and adequate.