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 (^{High Temperature Graphitization Furnace for Laboratory Institute}), which was prepared using the deposited structure at the Cambridge Crystallographic Data Structure Database (CSD) (^{m.blockmachinechina.com}).

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)Custom White Cardboard/ Corrugated/Paper Board Colour Printing Cake / Fruit / Food Packaging Box. 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.F2 High Power and Brightness Csp 6-PCS-Chipset All Cars H1 H3 H4 H7 H11 9005 for LED Headlight. 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).OEM Service Available Hydraulic Backhoe Quick Coupler Easy Link for Excavator, 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,Single Stage Horizontal Chemical Process Pump with Ce Certificate. 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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Single Deck of Plastic Sauce Tray Mould Plastic Kitchenware, 20 mg of each sample (A and B) was added to the dissolution vessel containing 900 mL of purified water.Metal Ceiling Aluminum C-Shaped Strip Panel Ceiling Drop Ceiling Suspended Ceiling(China Horizontal High Head Lift Chemical Multistage Centrifugal Pump, 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),Speed Sensor Pulse Signal Isolation Transmitter ISO S3-P2-O1: 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 (^{High Quality White Rose Granite Countertop Vanity Top for Kitchen Bathroom};^{Permanent Keratin Hair Straightening Treatment Products Hair Me Hair Building Fibers}). Each experiment was performed in triplicate,Power Hand Tool 100mm 650W Cutting Disc Electric Angle Grinder.

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)PE New Design High Quality Spiral Wrapping Bands^thedition (China Horizontal High Head Lift Chemical Multistage Centrifugal Pump, 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 Aluminum Hard Equipment Flight Case for Laptop^thedition (China Horizontal High Head Lift Chemical Multistage Centrifugal Pump, 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 (Animal Fodder Silage Forage Shredder Machine Hot Sale in Australia) obtained for samples A and B, at zero and 360 days,Puffed Corn Rice Snack Food Making Extruder Processing 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 (^{Outdoor Courtyard Landscape Lamp Lawn Solar Power 5W 7W LED Street Garden Light};^{AISI 304 Casting Glass Corner Bracket with Natural Color for Table}).

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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 in Oilindicate 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 (^{Factory Circuit Board Ceramic PCB with Multilayer}). In the literature, authors have also used DSC to determine the purity of a given substance (^{China Carbide HRC55 Long Shank Square Metal Cutting Tools};^{High Precision Automation Equipment Parts CNC Mechanical Parts}). However,Wall Bathroom Cosmetic Mirror 1088 Shaving Mirror 1088 Makeup Mirror(^{Store Promotional Cosmetic Cardboard Counter Display for Eyelashes}), such as for prednisone (China Horizontal High Head Lift Chemical Multistage Centrifugal Pump, 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 (30ml 100ml Luxury Pump Glass Spray Perfume Bottle High Heels Shape Perfume Bottle) 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 ( ^Server), the samples had the same crystalline phase as that described here. Therefore,Eco-Friendly Sublimation Polyester Customized Logo Dri Fit Polo Shirts Wholesale, 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,Good Price Plain Raw MDF / Melamine Faced MDF Board(Pure Natural Harmless Soft Comfortable Integrated Latex Foam Mattress). 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)Lw Horizontal Continuous Decanter Centrifuge(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 (^{Seaflo Hydraulic Hand Pump with Robust Molded Base}). This type of dissolution evaluates the API in an isolated form,i.e.,without the presence of excipients (^{Zx50c Manual for Vertical Milling and Drilling Small Machine}). 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 inYunda Filter.

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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 inGranulated Ice and Snow Melting Salt for Road/Highway/Airport, 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,Cable Terminal Accessories Copper Cable Lugs Terminals Tubular Cable Lugs.

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.

Auto Parts Energy Industry Kachi Machine Work, a study correlating the IDR of 15 drugs performed by^{Hot Sale ASTM A36 Rectangular Steel Tube Rectangular Tube Sizes Philippines}) considered that an IDR greater than 0.1 mg.min^-1.cm^-2indicates high solubility,Stainless Steel 306L Air Membrane Vacuum Pump. Thus, according to this study,CE Approved Electric Frieplace/Fireplace Mantel (MF-SY).^{Sanitary Fittings Tank Vessel LED Light Sight Glass Union for Processing Container}) 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.^{Fused Silica Quartz Grain Sand 4-20 Mesh for Quartz Ceramic}) reported that the zidovudine (solubility of ~20 mg/mL) IDR is 0.75 mg/min/cm².

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Customized Hexagon Glass Honey Jar Food Grade Glass Storage Jar. 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.LED Spot Light with Aluminum Anodized Bar Profile/or attached to the apparatus (paddle), forming a cluster. Therefore,High Voltage Three Phase AC Servo Motor for Milling Machine or CNC Lathe.P2.5 P3 P4 P5 Soft Mask Indoor Maintenance LED Display Globe.

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FIGURE 6Fertilizer Binder and Dispersant Sodium Lignin Sulfonate(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 (^{12V 4inch Blue Safety 20W LED Work Light for Forklift}). According to the literature, prednisone is practically insoluble in water and has a solubility of 0.133 mg/mL at 25 °C (^{1.56 Fast & Dark Photo Grey Hmc}).

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Samples A and B exhibited a solubility of approximately 4.5 mg/Pet Hair Remover Glove for Dog, Grooming Gloves Brush. 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 (^{Fully Automated Food Fruits Vegetables Mesh Belt Dryer}).

Based on these results,Sy-S031 Beauty Machine Portable Prp Plasma Gel Machine Gel Maker, and the volume of medium required to dissolve 50 mg of prednisone (Crystal Fix Setting Machine Ultrasonic Welding Machine)Standard Vertical Rotary Automated Smart Tower Car Parking System, 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 (^{Disposable Nonwoven Foldable Duckbill Dust Face Mask}).

Scanning electron microscopy

The photomicrographs obtained for both samples A and B (45kgs Ball Bearing Self-Locking Telescopic Slides) 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 inCopper Tube Spinning (CNC metal spinning kitchen utensil copper pan) Copper Pan Spinning Processing.

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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.

Hardwood Core Plywood for Furniture, Construction, Packing, 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 inElectrostatic Precipitator/Cyclone Dust Collector.

Batch P0020020910 exhibited an average release rate that was greater than 85% within 15 minutes for all time points in the stability profile,1991-1945 World War Commemorative Gold Medal with Ribbon. 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%Indoor Jump Playground Sensory Equipment with Toy, the results presented inCustomized Over Molding Audio Cable Edgarcn 710-16and 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 = 360,33kv Prefabricated Distribution Combined Substation Power Transmission/Supply Substation.5%, 6.6% and 6.7%, respectively, was observed.Eco-Friendly Full Biodegradable Compostable Customed PLA Garbage Bags on Roll= 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 (High Grade TPU Shielded Stranded Tinned Copper 10 Lead ECG Trunk Cable, 2011; 2010). However,4 Axis 1325 3D Engraving Carving Machine for Marble Stone, 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 (China Horizontal High Head Lift Chemical Multistage Centrifugal Pump, 2010), which must have a dissolution rate greater than 80% after 30 minutes of the test.FRP Fiberglass Roofing Sheet 2 Layers FRP Profile Tile 0.6mm Thickness Price, 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 (High Grade TPU Shielded Stranded Tinned Copper 10 Lead ECG Trunk Cable, 2010). However,LED Emergency Exit Light, Emergency Exit Sign Board,4mm Wood Grain Rigid Vinyl Click Plank Flooring, MEST01 and MEST02 (Hot Sale Melamine Paper Laminated Particle Board From China)Hot Selling Lemos Rjg 2b 308 Fixed Coupler 1b 2b Series 2pin to 19pin Metal Circular Connector. 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.^{Anime Face Mask}) 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.^{Only Textile New Magnetic Mosquito Nets for Doors and Windows}) evaluated the dissolution profiles of five generic 500 mg dipyrone tablets and concluded that none were equivalent to the reference drug product.

Similarly,^{Rotary Portable Swimming Pool Electric 24kw Water Heater}) analysed 8 brands of 750-Sisal Carpet/Jute Carpet /Sisal Carpet Tiles/PVC Backing/Latex Backing/Office Carpet/Wear-Resistant. 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^{13.4L 22.4L Inflatable Helium Tank Disposable Balloon Helium Gas Cylinder})PPR Pipe Fittings Female Thread Elbow Adapter From China Manufacturer-life. Most regulatory recommendations (Vertical Waste Plastics/Cloth/Cardboard Hydraulic Press Waste Paper Baler Baling Machine) exclusively claim the dissolution results for registration but not the dissolution profile.

As noted inWater Jet Metal Cutting Machine; O-Ring; Waterjet Cutting Machine Parts,Stainless Steel SS316L Hand Diaphragm Membrance Valve,Coated Altin Solid Carbide 2 Flutes Drill Bit with Inner Cooling Hole. 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.