Preparation and evaluation of gel emulsion with meloxicam

(I) Aim of the study Meloxicam is one of the most potent non-steroidal anti-inflammatory drugs, generally indicated for treatment of rheumatoid arthritis, osteoarthritis and juvenile arthritis and commercially available in form of tablets and suspension with recommended daily dose 7.5-15 mg. Unfortunately, long-term administration usually in higher doses is associated with increased risk of gastro-intestinal bleeding, cardiac arrest and stroke. An alternative approach to overcome these limitations is design of topical forms. The aim of this study is characterization and evaluation of gel-emulsion with meloxicam. (II) Materials and methods The present study is focused on elaboration of gel-emulsion composed of TEGO Carbomer 134 as gelling agent, propylene glycol as solubilizer, Tween 60 and Span 60 as emulsifiers, liquid paraffin as vehicle of oil phase from gel-emulsion, triethanolamine as pH adjuster and menthol as rubefacient whereby meloxicam is incorporated as free drug in oil phase. Prepared gel-emulsion was characterized for content, pH, spreadability, viscosity and microbial examination was performed. (III) Results and discussion Obtained results showed homogenous, easy spreadable, translucent gel-emulsion. Upon visual examination, no phase separation was observed. The percentage of drug content in gel-emulsion was 103%, spreadability was 9.2 cm and viscosity was 25 500 CP. Measured pH was 6.45 which is suitable for dermal application without risk of irritation. Additionally, absence of specific microorganisms tested was determined. (IV) Conclusion Even though gel-emulsion was stable and pharmacologically active for topical application, however, further investigations are needed in order to determine safety and security of developed formulation

Characterization of meloxicam loaded gel-emulsion

Meloxicam is one of the most potent non-steroidal anti-inflammatory drugs, generally indicated for treatment of rheumatoid arthritis, osteoarthritis, and juvenile arthritis and commercially available in form of tablets and solution for IV use with recommended daily dose 7.5-15 mg. Unfortunately, long-term administration usually in higher doses is associated with increased risk of gastro-intestinal bleeding, cardiac arrest, and stroke. An alternative approach to overcome these limitations is the design of topical forms. The aim of this study is characterization and evaluation of gel-emulsion with meloxicam. The present study is focused on elaboration of gel-emulsion composed of TEGO Carbomer 134 as gelling agent, propylene glycol as solubilizer and humectant, Tween 60 and Span 60 as emulsifiers, liquid paraffin as vehicle of oil phase from gel-emulsion, triethanolamine as pH adjuster and menthol as rubefacient whereby meloxicam is incorporated as free drug in oil phase. Prepared gel-emulsion was characterized by meloxicam content, pH, spreadability, viscosity and evaluation of microbiological quality. Obtained results showed homogenous, easy spreadable, translucent gel-emulsion. Upon visual examination, no phase separation was observed. The percentage of drug content in gel-emulsion was 103%, spreadability was 9.2 cm and viscosity was 25 500 CP. Measured pH was 6.45 which is suitable for dermal application without risk of irritation. Additionally, absence of the specific microorganisms Escherichia coli, Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus, Clostridia and Candida albicans was determined. The tested formulation was physicochemically stable and of adequate microbiological quality after three months of preparation, however, further research is needed to determine the safety of the developed gel-emulsion

Design of Experiments (DoE)-based approach for improvement of dry mixing processes in the production of low-dose Alprazolam tablets using Raman spectroscopy for content uniformity monitoring

A low-dose tablet formulation, containing a potent Benzodiazepine derivative Alprazolam was developed, considering the achievement of appropriate content uniformity of the active substance in powder blends and tablets as a major challenge. Two different types of lactose monohydrate (Tablettose 80 and Granulac 200) and two different types of dry mixing processes (high-shear mixing and "in bulk" mixing) were employed. To evaluate the influence of the variables (mixing speed, mixing time, filling level of the high-shear and cube mixer, lactose monohydrate type) and their interactions upon the response (content uniformity of Alprazolam in the powder blends), a Factorial 2 4 design (with 4 factors at 2 levels in 1 block) was generated for each type of mixer. For high-shear dry mixing the Response Surface, D-optimal Factorial 2 4 design (with 2 replications and 31 experiments) was used, while for the "in bulk" dry mixing the Response Surface, Central Composite Factorial 2 4 design (with 34 experiments) was used. The process parameters for the high-shear mixer were varied within the following ranges: filling level of 70-100%, impeller mixing speed of 50-300 rpm and mixing time of 2-10 minutes. For the cube mixer the following process parameter ranges were employed: filling level of 30-60%, mixing speed of 20-390 rpm and mixing time of 2-10 minutes. Raman spectroscopy in conjunction with a validated Partial Least Square (PLS) regression model was used as a Process Analytical Technology (PAT) tool for Alprazolam content determination and content uniformity monitoring. The DoE model was further employed to optimize the powder blending process in regard to the achievement of appropriate Alprazolam content uniformity using high-shear mixing and Tabletosse 80 as filler. The desirability function revealed that the following process parameters: a mixing time of 2 minutes, a mixing speed of 300 rpm and a 70% filling level of the mixer would produce powder blends with the lowest variability in Alprazolam content. The three independent lab batches of low-dose Alprazolam tablets, produced with high-shear mixing using these process parameters, conformed to the requirements of the European Pharmacopoeia for content (assay) of Alprazolam and uniformity of the dosage units

Characterization of Resveratrol Loaded Nanoparticles-A Review

Resveratrol (3,5,4-trihydroxy-transstilbene) is natural phenol and phytoalexin, extracted from red grapes, berries and cacao beans and found also in significant concentration in red wine. This active compound exhibited potent pleiotropic, antineoplastic activity without documented toxicity to normal cells. In addition, numerous studies reported that resveratrol, as most researched stilbene, possess numerous healthbenefit properties, such as cardioprotective, antidiabetic, neuroprotective and chemopreventive. Regretfully, clinical realization of resveratrol is restricted due to its poor aqueous solubility (0.05 mg/ml), degradation at physiological pH associated with extremely low systemic bioavailability. An intriguing strategy to overcome these limitations is formulation of resveratrol-loaded nanoparticles such as nanoemulsions, liposomes and solid-lipid nanoparticles as platforms for delivery to target tissue

Analysis of the consumption of drugs for the treatment of peptic ulcer and gastroesophageal reflux issued on prescription in a four - year period

Medicines indicated for the treatment of peptic ulcer and GERD are H2 blockers, proton pump inhibitors, antacids and mucoprotective agents. The analysis of the market of the medicines used for treatment of peptic ulcer and GERD, implies analysis of the range of these medicines registered in RNM, their presence on the list of medicines which costs are covered by the Health Insurance Fund, their financial and physical availability, as opposed to treatment recommendations of the above conditions according to MBD as well as a comparison of the range of these drugs available on the world markets. For the analysis of the consumptions of drugs issued at the expense of the Health Insurance Fund in pharmacies of the Republic of North Macedonia for a period of four years by number of realized prescriptions and total amounts of funds, we used the data published on the official website of the Health Insurance Fund of RNM. The increase in the total number of prescription drugs is probably due to the large number of patients diagnosed with peptic ulcer and GERD, as well as the recent regimen for issuing such medicines without a prescription. The total amounts for issued medicines at the expense of the Health Insurance Fund depend on the price and the number of issued prescriptions. The RNM is a county with a low standard and limited budget for medicine, in which the health policies are oriented towards saving the funds for procurement of drug

Good practice in cold drug supply chain

Pharmacy could not function without detailed, efficient, flexible and secure cold distribution chains, so in the future this would mean using more sophisticated delivery techniques and technologies. The cold chain consists of equipment and rules to ensure a constant temperature for thermo-sensitive products from their production to the time of use. Aim: The aim of this study is to evaluate data from WHO, EMA and FDA, their guidelines and directions, as well as relevant data from primary, secondary and tertiary literature. Method: In this paper we will review the regulatory measures and recommendations of the WHO, EU and US regarding the cold chain and will discuss the similarities and differences in their regulation. We summarized the reviewed literary data and sorted them according to the importance of the treated problem, made a comparison of the regulatory measures in order to ensure a safe cold chain and drew appropriate conclusions. Result: The reviewed documents do not show large and substantial differences in the approach to the cold chain and its importance for product safety. Conclusion: Drugs that require storage conditions under controlled temperature must be distributed in a way to ensure that their quality is not diminished

A Comparative Approach to Screen the Capability of Raman and Infrared (Mid- and Near-) Spectroscopy for Quantification of Low-Active Pharmaceutical Ingredient Content Solid Dosage Forms: The Case of Alprazolam

Content uniformity is a critical attribute for potent and low-dosage formulations of active pharmaceutical ingredient (API) that, in addition to the formulation parameters, plays pivotal role during pharmaceutical development and production. However, when API content is low, implementing a vibrational spectroscopic analytical tool to monitor the content and blend uniformity remains a challenging task. The aim of this study was to showcase the potentials of mid-infrared (MIR), near-infrared (NIR), and Raman spectroscopy for quantitative analysis of alprazolam (ALZ) in a low-content powder blends with lactose, which is used as a common diluent for tablets produced by direct compression. The offered approach might be further scaled up and exploited for potential application in the process analytical technology (PAT). Partial least square and orthogonal PLS (OPLS) methodologies were employed to build the calibration models from raw and processed spectral data (standard normal variate, first and second derivatives). The models were further compared regarding their main statistical indicators: correlation coefficients, predictivity, root mean square error of estimation (RMSEE), and root mean square error of cross-validation (RMSEEcv). All statistical models presented high regression and predictivity coefficients. The RMSEEcv for the optimal models was 1.118, 0.08, and 0.059% for MIR, NIR, and Raman spectroscopy, respectively. The scarce information content extracted from the ALZ NIR spectra and the major band overlapping with those from lactose monohydrate was the main culprit of poor accuracy in the NIR model, whereas the subsampling instrumental setup (resulting in a non-representative spectral acquisition of the sample) was regarded as a main limitation for the MIR-based calibration model. The OPLS models of the Raman spectra of the powder blends manifested favorable statistical indicators for the accuracy of the calibration model, probably due to the distinctive ALZ Raman pattern resulting in the largest number of predictive spectral points that were used for the mathematical modeling. Furthermore, the Raman scattering calibration model was optimized in narrower scanning range (1700–700 cm−1) and its prediction power was evaluated (root mean square error of prediction, RMSEP = 0.03%). Thus, the Raman spectroscopy presented the most favorable statistical indicators in this comparative study and therefore should be further considered as a PAT for the quantitative determination of ALZ in low-content powder blends.Scopu

Cost-effective quality control method for radiochemical purity of 99m Tc-Tectrotyd used in a Hospital Radiopharmacy unit

The new Radiopharmacy in Nuclear Medicine department in the Hospital and University Service of Kosovo apply the policy that all products administered into the human body, especially the new one are safe and show a constant high quality in producing the required effects. To ensure the efficacy of radiopharmaceuticals prepared at department in the Hospital and University Service of Kosovo, we introduced a cost-effective routine chromatographic method. The radiochemical purity (RCP) of 99m-Technetium labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In a new hospital radiopharmacy unit it may not be possible to use compendial analytical methods or expensive equipment for radiochemical purity analysis, but all radiochemical analysis methods should however be validated against compendial or otherwise proven methods. Our goal was to optimize the radiolabeling protocol for the regular use of 99m Tc-Tektrotyd and to establish chromatographic method for quality control after labelling as a part of our daily diagnostic procedures for assessment of NET patients labelled with 99m-Technetium was for the first time used to identify medical problems related to overexpression of somatostatin receptors, particularly subtype 2 and, to a lesser extent subtype 3 and 5. Methods: Tektrotyd or HYNIC – (D-Phe1, Thyr3-Octreotide) trifluoroacetate (Polatom) radiopharmaceutical were reconstituted with about 2 000 MBq of freshly eluted sodium pertechnetate as described by the manufacturer and spiked with eluate of the same generator to obtain a range of impurity concentrations. Samples of technetium- 99m Tektrotyd were spotted on 1x15 cm ITLC-SG strips and developed in appropriate mobile phases described by the manufacturer. Each strip was immediately cut into 30 pieces of 0.5cm and the radioactivity of each piece was measured in a dose calibrator (Capintec,Inc). The percentage of RCP for each ITLC strip was calculated using the total the radioactivity and the radioactivity from each segment as the total present radioactivity from which the basic radioactivity was subtracted. The present plotted radioactivity in the obtained peaks corresponded to the distribution of radioactivity, i.e. to the present complex of 99mTc Tektrotyd. Results and Discussion: The proposed method proved to be accurate and precise within the RCP range of approximately 90% to 100% in comparison of the producer requirements. Conclusion: The proposed method is suitable as a reliable low-cost method for limited resource settings and small hospital radiopharmacy unit