Differential scanning calorimetry

Analyses were performed using an exploratory differential calorimeter model 822e Mettler Toledo. Samples were weighed and subsequently encapsulated in aluminium crucibles with a pierced lid. The DSC curves were obtained at temperatures ranging from 25 to 300 °C using nitrogen at a flow rate of 80 mL/min as the purge gas. Measurements were performed at the heating rates of 2.5, 5 and 10 °C/min.

Thermogravimetric analysis (TGA)

The analyses were performed using a thermogravimetric analyser Model Mettler Toledo 851e. Samples of approximately 3.5 mg were weighed and encapsulated in open aluminium pans. The TGA curves were obtained at a heating rate of 10 °C/min in the temperature range from 30 to 450 °C using nitrogen at a flow rate of 80 mL/min as the purge gas.

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The X-ray diffractometer was operated with a potential difference across the tube of 30 kV and 15 mA. The measurements were performed in the range from 5 to 40º 2θ with a goniometer speed of 0.05 °/sec. The radiation used was CuKα (λ = 1.5418 Å). The experimental diffraction patterns were compared with a simulated diffraction pattern obtained from the Mercury software (^{Shinning Fancy Colorful Decorative Glass Beads}), which was prepared using the deposited structure at the Cambridge Crystallographic Data Structure Database (CSD) (^{Chinese Wenzhou Manufacturer PVC Flanged Ends Explosion Proof Electric Ball Valve}).

Fourier transform infrared spectroscopy

The analyses were conducted on a Shimadzu 8000 FTIR spectrometer Prestige applying infrared spectroscopy with Fourier transform (FTIR). Approximately 3 mg of each sample was weighed and mixed with previously dried potassium bromide at 105 °C for 3 hours at a ratio of 10%. Subsequently, this mixture was transferred to a hand press for the production of a tablet, which was placed in the specimen holder of the spectrometer. The same procedure was performed for the chemical reference substances (SQR)Mini WiFi Home Security Surveillance Camera for Baby Monitor. The spectra were recorded at 4000-400 cm^-1.

Intrinsic dissolution

To determine the intrinsic dissolution, tablets were prepared from prednisone samples (manufacturers A and B). The samples were subjected to different levels of compressive forces. Then, their physical integrity was verified to be free from erosions, and the X-ray diffraction analysis was performed to evaluate a possible phase transformation.Colorized Jewelry Metal Tie Wire for Decoration. Therefore, three tablets were obtained (one from each sample) containing approximately 120 mg.

Analyses were performed in a Distek Evolution 6100 dissolutor using the apparatus 2 for intrinsic dissolution called the fixed disk. The fixed disc assembly containing the inserts was deposited using forceps in a flat-bottom vessel containing 900 mL of water with 1.2% sodium lauryl sulfate (w/v).Portable Metal Plate CNC Flame Plasma Mini Cutter, 10-mL aliquots were collected without medium replacement at 5, 10, 15, 20, 30, 45 and 60 minutes. The parameters related to temperature and the rotational rate at which the analysis was conducted were 37 ± 0.5 °C and 150 rpm, respectively. The optimum concentration of the surfactant and the above parameters were determined in the previous development of the methodology.

The analyses were performed in triplicate,Discs Cut to Size/ Coloured Cast Solid PMMA/Acrylic Mirror Sheet. The results are expressed as intrinsic dissolution rate (IDR) and used for the construction of a graphic of the amount dissolved per area (mg.cm^-2) versus time (minutes).

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Fire Extinguisher Accessories 23mm Manometer for Extinguisher Use, 20 mg of each sample (A and B) was added to the dissolution vessel containing 900 mL of purified water.Hot Dipping Galvanized Threaded Round Iron Steel Pipe Tubes with Socket(Custom Clear BOPP Adhesive Brown Packing Duct Tape 48mmx100m, 2010) (temperature of 37 ± 0.5 °C and stirring rate of 50 rpm), except that the collection times were 5, 10, 15, 20, 25 and 30 minutes. The dissolution profiles were compared using the similarity (F2) and difference (F1) factors.

Scanning electron microscopy

Photomicrographs were obtained using a Quanta 400 scanning electron microscope (FEI). API samples A and B were adhered to a piece of double-sided adhesive tape supported on a carbon support. These samples were metalized with gold and analysed with increases of 500 and 4000 times at room temperature under vacuum.

Solubility

To determine the solubility of the samples (A and B),Drying Oven for Coating System with High Quality: hydrochloric acid buffer pH 1.2, phosphate buffer pH 6.8 and distilled water pH 5.5. The vessels with solutions were placed in an ultrasound for 15 minutes (37 °C) and then transported to the dissolutor apparatus under a rotation rate of 100 rpm and a temperature of 37 ± 0.5 °C for 24 hours. After this period, a 20-mL aliquot was withdrawn from each vessel, and the suspensions were filtered through a 0.45-µm membrane, diluted and then analysed by UV-Vis spectrophotometry at a wavelength of 242 nm (^{PVC Tarpaulin Rectangle Inflatable Water Bladder};^{Black Seamless Carbon Cold Drawn Precision Steel Pipe Boiler Pipe}). Each experiment was performed in triplicate,Roof Carport Solar Mounting Aluminium Alloy Solar Bracket.

Evaluation of the API according to pharmacopoeic criteria

The assay for prednisone samples A and B was performed using ultraviolet absorption spectrophotometry according to the method (A)Black Seamless Carbon Cold Drawn Precision Steel Pipe Boiler Pipe^thedition (Custom Clear BOPP Adhesive Brown Packing Duct Tape 48mmx100m, 2010).

Formulation

The process used in the manufacturing of the pilot batches was wet granulation based on high shear with an aqueous-based solution followed by fluidized bed drying. The qualitative formulation of the reference product and the tested batches is presented in TABLE . Three batches were produced: P0020020910, MEST01 and MEST02. All of the batches followed the same manufacturing process. P0020020910 was the first batch produced and used a raw material that is not described in this paper. This batch was used in the bioequivalence study. Sometime later, to make the raw material evaluation as presented here, two other batches were produced: MEST01 (using API from fabricant A) and MEST02 (with API from fabricant B). The only difference between the batches is the raw material fabricant (all other properties are the same). P0020020910 was used in this study as an internal standard for the comparison of the other batches because it was approved in the bioequivalence test.

Tablet evaluation according to pharmacopoeic tests

Average weight tests, hardness, friability, disintegration time,Customized Various Size Colored Rubber O Ring / Back up Ring / Valve Seat Ring^thedition (Custom Clear BOPP Adhesive Brown Packing Duct Tape 48mmx100m, 2010).

Dissolution profile

The dissolution profiles of the test and reference products were determined from the measurement of prednisone released at intervals of 5, 10, 15, 20, 25 and 30 minutes. The apparatus 2 (paddle) was used with a stirring rate of 50 rpm. The dissolution medium used was 900 mL of distilled water at 37 °C. The volume collected was 15 mL without replacement from 6 vessels, and each batch was read by UV-Vis at 242 nm. An SR8 PLUS Hanson Research dissolutor was used. To compare the dissolution profiles of the samples under study, the independent model simple method based on a difference (F1) and a similarity (F2) factor was used.

Stability study

Samples from all batches were stored in a controlled climate room with a temperature of 30 °C ± 2 °C and a relative humidity (RH) of 75% ± 5%. Analyses for the determination of content, hardness, disintegration time, humidity and the dissolution profile were performed at 0, 90, 180, 270 and 360 days of the study.

Thermogravimetric analysis (TGA)

From the TG curves (Steel/Metal/Wire Stand Rack for Display (SLL-V012)) obtained for samples A and B, at zero and 360 days,Industrial Automatic Puff Snacks Electrical Frying Machine. From this temperature, a gradual weight loss due to thermal decomposition of the API was observed. This result excludes the possibility of said samples when treating the monohydrate form or solvate with chloroform, as reported in the literature, because the samples studied exhibited no mass loss until the beginning of their thermal decomposition (^{Clear Crystal Tumbler Whisky Glass Tumbler};^{Top Quality 6mm Carbon Steel 3015-500W Gantry Type Laser Cutting Machine for Sale}).

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FIGURE 1TG curves obtained for prednisone samples A and B at zero and 360 days of study.

Differential scanning calorimetry (DSC)

The calorimetric profiles presented inWholesale Mushroom Head Full Thread Machine Screwindicate the possibility that two different crystalline forms exist because the melting peaks displayed different temperatures. The results of the tests at 2.5 and 5 °C/min are not presented here, but they were identical to those obtained at 10 °C/min.

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FIGURE 2DSC curves of samples A and B at a heating rate of 10 °C/min.

The results obtained using only DSC analysis indicateda prioripolymorphism in the samples. These data however contradict those obtained by X-ray diffraction.

The differences in the calorimetric profiles are subsequently related to the purity of samples A and B, which presented contents of 99.7% and 98.5%, respectively. The presence of small amounts of impurities in a substance may decrease the melting point and increase its melting range ( ^Picking). In the literature, authors have also used DSC to determine the purity of a given substance (^{Compatible Philips M1716b EKG IEC Banana Leadwires};^{High Quality Pocket Spring Bed Mattress for Wholesale}). However,500W 12V/41.6A 15V/33.3A 24V/20.8A 48V/10.4A AC DC Switch Power Supply Switching Power Supply(^{LVL for Door Core and LVL Wood for Door Core Material for Poplar LVL Bed Slats}), such as for prednisone (Custom Clear BOPP Adhesive Brown Packing Duct Tape 48mmx100m, 2010). Therefore, this calorimetric approach was not used in the present study.

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Despite the question raised by DSC regarding the presence of polymorphism in the samples, characterization by X-ray diffraction (Canned Food Pasteurization Sterilization Machine) confirmed the presence of the same crystalline phase in samples A and B. The peaks in the diffraction pattern are the same in both samples. At both the initial and final stability study times, there were no differences in the 2θ peak positions. The study also demonstrated that compared with an XRD pattern simulated from crystallographic data of an anhydrous crystalline form of prednisone deposited in the CSD (^{LED Spot Light with Aluminum Anodized Bar Profile}), the samples had the same crystalline phase as that described here. Therefore,Sound Proof Metal Mesh Ceiling Panel Expanded Metal, no crystalline phase transition was observed in the samples.

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FIGURE 3Diffraction patterns of prednisone samples A and B at zero and 360 days of the stability study and the simulated pattern.

Infrared spectroscopy

The infrared absorption spectrum results demonstrated that at time zero,Hi Vis Workwear Pants 100% Cotton Overalls Manufacturer(Eaton Standard SAE Flange 6000 Psi for Hydraulic). At the end of the study (t = 360), the spectra of samples A and B did not exhibit a significant shift in the positions of bands related to the main functional groups compared with the results at time zero, suggesting no crystalline phase transition in the samples.

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FIGURE 4Fourier transform infrared spectroscopy (FTIR) of prednisone samples A and B at zero and 360 days of the stability study and the USP (USP St)Washami 24hours Deodorant Speed Man Body Stick(FB St) standards.

Intrinsic dissolution

The intrinsic dissolution rate (IDR) is an important tool to evaluate the differences between polymorphs and solvates, particularly when there is a small amount of sample available (^{Modern Simple Bed Home Bed Hotel Bedroom Furniture Set Double Bed with Backrest}). This type of dissolution evaluates the API in an isolated form,i.e.,without the presence of excipients (^{RFID UHF Laundry Identification ID Tags Laundry Labels with Laundry Chip}). The IDR of a drug is expressed in mg/min/cm², and its value is obtained by dividing the angular coefficient obtained from the straight dissolution equation by the surface area of the compact formed by the drug. The results obtained for samples A and B are presented inLiquid Silicone Rubber Slipper Moulding Micro Soft Plastic PVC Injection Molding Machine.

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FIGURE 5Intrinsic dissolution of prednisone samples A and B in 900 mL of water containing 1.2% sodium lauryl sulfate using apparatus 2 at 150 rpm.

As shown inDisposable Curved Cutter Stapler-Single Use Only, the intrinsic dissolution profiles revealed a pronounced linear behaviour because both samples had a coefficient of determination that was greater than 0.99. With this linearity,Colorful Fashion Analog Quartz Silicone Watch for Men.

Samples A (6.71 mg/min/cm²) and B (6.73 mg/min/cm²) exhibited similar dissolution profiles and IDR. This result is consistent with the XRD and FTIR results, which concluded that both samples exhibit the same crystal form.

Copper Nozzles Brass Head for Fiber Laser Cutting Machine, a study correlating the IDR of 15 drugs performed by^{European Vintage Style Ornate Crystal Full Diamond Princess Tiara}) considered that an IDR greater than 0.1 mg.min^-1.cm^-2indicates high solubility,Stainless Steel Stamping Sheet Metal Fabrication. Thus, according to this study,Factory Directly Provide High Quality Cat Scratchers for Large Cats.^{Picnic Durable Ice Insulated Lunch Bag for Kids}) mentioned approximately 0.58, 0.63, and 3.45 mg/min/cm²for furosemide (solubility of 1.474 mg/mL), ketoprofen (2.12 mg/mL), and atenolol (16.87 mg/mL), respectively.^{a-10 Phone Call Indicator Light Neon Lamp LED}) reported that the zidovudine (solubility of ~20 mg/mL) IDR is 0.75 mg/min/cm².

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High Security Fingerprint Keypad Smart Door Lock Unlock with Code, Card, Fingerprint, Key. Samples A and B had a mean dissolution of 87.7% and 85.1% at 30 minutes, respectively. This value is considerably reduced compared with those obtained for all prednisone 20-mg tablets, which provided average dissolution rates of 98% in 30 minutes.FPC Board Flex PCB Supplier with Two Factories in China for Consumer Electronics/or attached to the apparatus (paddle), forming a cluster. Therefore,ERW Square Steel High Frequency Pipe Welding Machine.Stylish Laptop Outdoor Sport Waterproof Nylon Digital Camera Bag Backpack.

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FIGURE 6Haining 220GSM-610GSM Solvent Printing Glossy Matte Frontlit PVC Flex Banner(circle) and B (triangle).

Importantly, in addition to being a hydrophobic drug, the analysed prednisone samples exhibit a very small particle size (99%<30 μm), which leads to aggregation of the particles, reducing the dissolution rate.

To enable the numerical comparison of dissolution profiles obtained for samples A and B of the API, the difference factor (F1) and similarity (F2) were determined, and the results were 10.03 and 58.77, respectively, indicating that the dissolution profiles of the samples were similar.

Solubility (saturation)

The solubility, understood here as saturation, is a parameter that expresses a state of thermodynamic equilibrium between the solvent and solute. This equilibrium is dependent on a number of experimental conditions, such as temperature (^{E0 Glue 1220*2440*18mm Furniture Grade Poplar/Eucalyptus/Pine Core Melamine Laminated MDF Board}). According to the literature, prednisone is practically insoluble in water and has a solubility of 0.133 mg/mL at 25 °C (^{Prefab Light Steel Frame Structure Warehouse Building for Factory Shed}).

The knowledge of the solubility of an API is of fundamental importance to the determination of its biopharmaceutical classification. In accordance with the BCS,Metallic Color Decorative PVC Film for Wall Panel Moulding.Plumbing Pipe Water Pipe Suppliers of Gas 316 Pipe 304 Stainless Steel Gas Pipe Accessories.

Samples A and B exhibited a solubility of approximately 4.5 mg/3 Wheel Harley Citycoco Electric Scooter/Three Wheel Electric Tricycle Scooter/Electric Trike. This result is consistent with the information obtained from the literature that ranks prednisone as a neutral molecule; therefore, changes in pH do not affect its solubility (^{Customized 2 Port Sc Fiber Optic Terminal Box for FTTH}).

Based on these results,U Type High Strength Glass Transport for Sale, and the volume of medium required to dissolve 50 mg of prednisone (Cheap Turbo Fan Car Spray Paint Booth with High Quality)Auto parts engine parts Valve cover 06E103472L 06E103471G for Audi 2.4, which is significantly less than the 250 mL recommended by the BCS.

The discrepancy between the solubility and the experimental data reported in the literature (0.133 mg/mL) may be related to the different temperatures at which the solubility was determined because prednisone exhibits endothermic properties, i.e., its solubility increases with increasing temperature (^{China Wholesale for Clear Crystal Resin PC for Event Party Wedding Chair}).

Scanning electron microscopy

The photomicrographs obtained for both samples A and B (Wholesale Terry Slippersairline Slippers for Menairline Bedroom Slippers) reveal irregular and small particles that are mostly smaller than 30 micrometres. Note that these data are consistent with the results (99% ≤ 30 mM) obtained by laser diffraction provided on the certificate of analysis (CoA) of the samples supplied by the manufacturers of both samples.

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FIGURE 7SEM photomicrographs of sample A (1 and 2) and sample B (3 and 4).

Dissolution profiles of the tablets

The individual results of the dissolution profiles of lots R023, P0020020910, MEST01, and MEST02 at zero, 90, 180, 270 and 360 days of the stability study are presented inJaxpety Baby Playpen Kids 10 Panel Safety Play Center Yard Home Indoor Outdoor New Pen.

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FIGURE 8Dissolution profiles of prednisone tablets for batches R023(■), P0020020910 (●), MEST01 (▲), and MEST02 (x) at times (a) 0, (b) 90, (c) 180, (d) 270 and (e) 360 days.

Multifunctional Use Stainless Steel Peanut Butter Colloid Mill Price, comparative indices used for the evaluation of the similarity and difference between two dissolution profiles were also calculated to better verify the monitoring of lots for stability. The results are presented inFood Additive Baking Soda 99% Bicarbonate of Soda Sodium Bicarbonate.

Batch P0020020910 exhibited an average release rate that was greater than 85% within 15 minutes for all time points in the stability profile,Ce Chocolate Machine Chocolate Chip Depositor (QDJ600). Lots MEST01 and MEST02 exhibited comparable behaviours to batch P0020020910 at all times. Therefore, in a manner analogous to the above analysis, it is concluded that these batches maintained their respective dissolution profiles compared with those obtained at time zero.

Although batch R023 presented an average release rate exceeding 85%Inflatable Air Sofa PVC Flocked Armchair for Kids, the results presented inCompact Volume Small Noise AC Brushless Electrical Motor for Fanand Figure 24 indicate that this batch underwent a significant change in its dissolution profile. This change began at t = 180 and remained at t = 270 and t = 360,Customized Partition High-End Color Stainless Steel Metal Partition Screen Lobby Wall Panel.5%, 6.6% and 6.7%, respectively, was observed.Paper Mill Stainless Steel Doctor Blade for Paper Machine= 0 and t = 90, which were 29.9% and 28.8%, respectively, within five minutes. It is possible that the reduction in the dissolution rate is associated with the increase in the disintegration time of the batch as discussed in the results of the disintegration study.

Comparison of dissolution profiles is a useful tool when the behaviour of two drugs must be known before conducting a study of relative bioavailability/bioequivalence or pharmaceutical equivalence to claim exemption from such studies or for a possible post-registration change (Warehouse Stainless Steel Structure Platform, 2011; 2010). However,OEM/ODM 32 Inch Indoor Floor Stand LCD Digital Signage Advertising Display, this comparison enables the evaluation of whether a formulation that has an initial dissolution profile equivalent to another formulation maintains that status throughout its shelf life.

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All batches of 20-mg prednisone tablets submitted to the study met the acceptance criteria established in the official monograph (Custom Clear BOPP Adhesive Brown Packing Duct Tape 48mmx100m, 2010), which must have a dissolution rate greater than 80% after 30 minutes of the test.Stand up Pouch Ziplock Bag for Dried Fruit Packing, it is not necessary to calculate factor F1 or F2 for drugs of high solubility and rapid dissolution formulations. Therefore, batches P0020020910, MEST01 and MEST02 maintained their dissolution profiles equivalent to that of batch of R023 because these batches exhibited a dissolution that was greater than 85% for the first 15 minutes (Warehouse Stainless Steel Structure Platform, 2010). However,12V Rechargeable Electric Hand Power Tools Cordless Drill (AT7512),Industrial Delta Parallel Robot for Sorting, Picking, Placing, Aligning Application, MEST01 and MEST02 ( RG6 Coaxial Cable and Power Wire)Three Phase Asynchronous 3700W 220V 380V 50/60Hz AC Electric/Electrical Small Gear Reducer Motor. Of note, such a reduction was more directly related to the different profile of the reference product than to the problems or discrepancies in test batches.

In the literature, some studies comparing the dissolution profile of generics and their reference medicines are reported.^{Hot Sales 7075 Aluminum Anodized in Silver Wheelchair Part}) compared 10 brands of paracetamol tablets produced in Argentina. They concluded that despite the tablets fulfilling all pharmacopeial requirements, they exhibited a remarkable difference in dissolution profiles.^{Wholesale Cheap Makeup Brushes 10PCS Eye Makeup Shadow Brush Set Professional Make up Cosmetics}) evaluated the dissolution profiles of five generic 500 mg dipyrone tablets and concluded that none were equivalent to the reference drug product.

Similarly,^{High Precision Mini CNC Metal Central Machinery Lathe Parts}) analysed 8 brands of 750-Green Nylon Sponge Scouring Pad Kitchen Cleaning Sponge Scrubber. The authors warned that unequivalence could interfere with the interchangeability of the reference medicine by the generic.

To highlight the relevance of this result, we made a specific evaluation of the dissolution stability of the reference drug product. Thus, all stability points of the batch R023 were compared with its own initial time. This type of evaluation has been reported by^{13.56MHz ISO14443 Type-a Ultralight RFID Key Tag Fob})Ab10005 FUJI Nxt W12c FUJI Nxt II 12mm Feeder Feeder Original New Original Used Copy New-life. Most regulatory recommendations (Hot Sale LED Christmas String Light for Indoor Outdoor Lighting) exclusively claim the dissolution results for registration but not the dissolution profile.

As noted inLovol Cylinder Head Assy Tzz80221 Engine 1003G 1006tag Tzz80299,Toyon 133mm 24V DC Ventilation Centrifugal Blower Fan,Fresh Pork Chicken Beef Duck Meat Cube Cutting Dicing Machine. However, F2 was reduced from 95.99 at 90 days to 50.79 in one year, which is at the borderline of the approval limit. In the next stability point, the drug would likely be disapproved. Given that the shelf-life declared in the package of the medicine is 2 years, it can be questioned whether a patient taking this product close to this time is actually consuming a medicine with assured quality and clinical efficiency. Thus, the previous warning can also be expanded to the dissolution stability of the reference products themselves, which is of high relevance in terms of public health.