Ground Tablets Research Articles

Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets

PurposeVenetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets. MethodsAn open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing. FindingsThe crushed and ground tablets met the bioequivalence criteria (0.80–1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUCt) and to infinite time (AUCinf) but exhibited a slightly lower maximum plasma concentration (Cmax). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity. ImplicationsCrushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding. ClinicalTrials.gov identifiersNCT05909553, registered June 12, 2023.

Photochemical stability of warfarin potassium in powdered pharmaceutical tablets

Warfarin potassium (Wf) commercial tablets originally formulated for adults are ground before administration to pediatric patients and elderly patients with dysphagia. The present study investigated the effect of tablet grinding on the photostability of four types of commercial Wf tablets and predicted the photostability of the tablet powders by chemometric analysis. The photodegradation of Wf content was evaluated by reversed-phase column high-performance liquid chromatography with ultraviolet (HPLC-UV). The bulk Wf powder was relatively photostable, whereas ground Wf tablets underwent substantial photodegradation. The photostability of the ground powders of a brand-name Wf commercial tablet and three generic Wf commercial tablets was quantitatively assessed and compared. In certain cases, the Wf in all the three ground generic tablets was less photostable than in the ground brand-name tablets. After 28 days of light irradiation, the Wf content decreased to 69.79% in the brand-name tablets, while it was 31.90% in some generic tablets. To clarify the factors influencing the relative photostability in various Wf formulations, we analyzed the intermolecular interactions between the active ingredient and the excipients by partial least-squares regression analysis based on photostability screening for each additive. The results suggested that the additives light anhydrous silicic acid and povidone adversely affect the stability of Wf tablets. In addition, the light stability of ground tablets was affected considerably by their formulation.

Efficiency of extraction and conversion of pseudoephedrine to methamphetamine from tamper-resistant and non-tamper-resistant formulations

Clandestine chemists have demonstrated an ability to convert commercially available pseudoephedrine formulations to methamphetamine. Some of these formulations have properties that manufacturers claim limit or block the extraction of pseudoephedrine and its direct conversion to methamphetamine. In this study, 3 commercially available pseudoephedrine formulations were evaluated for ease of extraction and conversion to methamphetamine using a common chemistry technique called the one-pot method that is frequently employed by clandestine chemists. Two marketed pseudoephedrine formulations with claimed tamper-resistant properties – Zephrex-D® and Nexafed® – were compared to Sunmark®, a comparator formulation of pseudoephedrine without tamper-resistant properties. Particle size reduction was conducted using 8 readily available tools; solubility was assessed using 2 common aqueous solutions and various reaction conditions (e.g., temperature, stirring); extractability was evaluated using 8 common organic solvents. The one-pot (single vessel) method commonly used in clandestine processes was employed; chemicals and equipment were purchased locally on the open market. Quantities and addition times of the chemicals used to carry out the procedure and the duration of the reaction were varied to determine the effect on methamphetamine yield. The procedure was appropriately scaled and conducted in a controlled environment to reduce risk and maximize yields. Pseudoephedrine and methamphetamine were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Standard quantitative procedures were used to determine the quantities of pseudoephedrine and methamphetamine recovered and produced, respectively. Particle size reduction resulted in some loss of material of each pseudoephedrine formulation; Zephrex-D tablets were broken down to a coarse material; Nexafed and Sunmark tablets were reduced to a fine powder. The solubility rates of intact and ground tablets varied by product; Zephrex-D was most resistant to solubilizing while Nexafed and Sunmark were comparable and dissolved completely, demonstrating no solubility-resistant properties. Conditions of the one-pot method were modified throughout the studies to increase methamphetamine yield. Using optimal parameters identified in these studies and allowing the reaction to proceed for 90 min, average percent conversions were similar for the 3 formulations: 43.3% for Zephrex-D, 46.4% for Nexafed, and 48.6% for Sunmark. The greatest conversion occurred with a 150 min reaction time and resulted in 44.8%–48.4% conversion of Zephrex-D, 54.1%–66.4% conversion of Nexafed, and 58.6%–71.8% conversion of Sunmark. This series of methodological evaluations demonstrated that clandestine chemists can readily produce similar yields of methamphetamine using pseudoephedrine products with and without claimed tamper-resistant technology.

(404) Extraction testing of a novel extended-release, abuse-deterrent formulation of morphine, Morphine ARER, in common household solvents

Abusers of prescription opioids commonly extract the active ingredient from non-abuse deterrent, extended-release formulations to bypass the intended slow release characteristics and increase the opioid’s bioavailability for injection, smoking, or oral administration. Abuse deterrent products are designed to increase the hurdles required to extract the active ingredient with the ultimate goal of decreasing the misuse and abuse of these formulations for all routes of administration dependent on extraction. The FDA’s Draft Guidance for Industry, Abuse-Deterrent Opioids – Evaluation and Labeling (January 2013) recommends that laboratory-based in vitro manipulation and extraction studies be performed to evaluate the physical characteristics of a novel product and to guide the downstream pharmacokinetic (PK) and clinical abuse studies. To assess the abuse deterrent properties of an investigational extended-release formulation of morphine, Morphine ARER, in vitro laboratory testing was performed to assess the extractability of morphine. Five intact and five finely crushed tablets were dissolved in 30 mL of household solvents including water, saline solution, vinegar, coke, pH 2, pH 4, pH 6, pH 10, 5% ethanol, 10% ethanol, 20% ethanol, 40% ethanol, and 90oC water. The percent of morphine released was assessed via liquid chromatography. Morphine ARER did not dose dump morphine under any condition or solution. Water was found to be the best solvent for extraction. Interestingly, the amount of morphine released was largely similar between crushed and intact tablets and reduced in increasing concentrations of ethanol. These data clearly indicate that Morphine ARER was highly resistant to extraction and did not result dose dumping either from intact or ground tablets, even at 30 minutes, which is longer than an abuser would be expected to wait. Funding Provided by Inspirion Delivery Technologies LLC.

Investigating the properties of subcritical water extraction with pharmaceutical tablets

The properties of subcritical water extraction (SWE) in the sample preparation of pharmaceutical tablets were investigated. Tablets comprised of microcrystalline cellulose excipients broke apart up to 80 times faster in subcritical water than they did in room temperature water, while those containing starch readily broke apart in either. Tablets containing starch were also observed to gelatinize or “paste” over several SWE conditions, impeding subsequent filtration and analysis. This effect was avoidable, however, since it was demonstrated to disappear with increases in extraction time and temperature or decreases in sample size. Using SWE, two common over-the-counter pharmaceuticals were extracted under optimized conditions from tablets comprised of either microcrystalline cellulose or starch excipients. Analyte recoveries of 95% or more were obtained at 150 °C for vitamin C (ascorbic acid) tablets in as little as 8 min for the extraction of a whole intact tablet, 6 min for two half tablets, and 5 min for a ground tablet. By comparison, this occurred at 250 °C in just 2 min for an intact slice of an acetaminophen tablet. Reproducibility was generally quite good with these trials producing RSD values of less than 2%. The results indicate that SWE can be a potentially viable and efficient method for the sample preparation of whole, sliced, or ground pharmaceutical tablets, and further exploration of this approach is promising.

Simple UV Spectrophotometric Assay of Metronidazole

Metronidazole is a derivative of benzimidazole. It is being used widely for the treatment of amoebiasis. An efficient, simple and least time consuming spectrophotometric method for the assay of metronidazole has been developed. Comparison of assay of three different brands of metronidazole has also been available in public medical stores of Karachi, Pakistan. The assay is based on the ultraviolet UV absorbance maxima at about 340 nm wavelength of metronidazole using water as solvent. A sample of drug was dissolved in water to produce a solution containing metronidazole. Similarly, a sample of ground tablets of different brands were dissolved in water and various dilutions were made. The absorbance of sample preparation was measured at 340 nm against the solvent blank and the assay was determined by comparing with the absorbance of available brand. The method can be applied for the routine QC quantitation of metronidazole in tablet formulation actively.

Signal intensity of lanthanum carbonate on magnetic resonance images: phantom study

Lanthanum carbonate (LC) is used to treat hyperphosphatemia. The purpose of this study was to investigate the signal intensity (SI) of LC on magnetic resonance imaging (MRI) scans of phantoms. LC tablets were thoroughly ground and mixed with distilled water or edible agar (0.05, 0.25, 0.5, and 2.5 mg/ml) in plastic bottles. Four intact tablets were placed in plastic bottles that did or did not contain distilled water or agar. Two radiologists consensually evaluated T1- and T2-weighted images (WIs) obtained with 1.5- and 3.0-T MRI systems for the SI of unground and ground tablets. On T1- and T2WI, the SIs of the LC suspensions and the solvents alone were similar; the SIs of unground tablets alone and of the air were also similar. Unground tablets in phantoms filled with solvent exhibited lower SI than the solvent. Ground tablets in suspension were not visualized on MRI or computed tomography. These results remained unchanged regardless of differences in magnetic field strength or the solvent used. Ground LC had no contrast enhancement effect on T1WI; on T2WI it did not affect the SI of the solvent. Unground LC tablets may be visualized as a "filling defect" on MRI.

UV Spectrophotometric Method for Assay of the Anti-Retroviral Agent Lamivudine in Active Pharmaceutical Ingredient in its Tablet Formulation

A rapid, simple, accurate, and economical spectrophotometric method has been developed and validated for the assay of the anti-retroviral agent lamivudine in active pharmaceutical ingredients (API) and in its tablet formulation. The analysis is based on the UV absorbance maxima at about 270nm wavelength of lamivudine, using methanol as solvent. A sample of API was dissolved in methanol to produce a solution containing 10 µg/mL of lamivudine. Similarly, a sample of ground tablets were extracted with methanol, centrifuged, and diluted with the same solvent. The absorbance of the sample preparation was measured at 270 nm against the solvent blank, and the assay was determined by comparing with the absorbance of a similarly prepared 10 µg/mL standard solution of lamivudine. The calibration graph was rectilinear from 5 µg/mL to 15 µg/mL for lamivudine with the correlation coefficient being more than 0.999. The relative standard deviation of the replicate determination was about 0.5%. The percent recovery was within the range of 98%–102%, indicating insignificant interference from the other ingredients in the formulation. The method can be applied for the routine QC quantitation of lamivudine in API and tablet formulation.

Hypothyroidism Talking Points 2006

In 1603 Paracelsus described endemic cretinism. Over 150 years later, in 1878, Ord proposed the term myxedema to describe the clinical features of the “‘cretinoid’ affection occasionally observed in middleaged women”. In 1883, Emil Theodor Kocher reported myxedema after thyroidectomy. This led to a 1909 Nobel Prize in Medicine “for his work on the physiology, pathology and surgery of the thyroid gland.” Modern endocrinology’s birth followed in 1891 when Murray injected sheep thyroid extract into a patient with myxedema. Just one year later injection was replaced by “eating ground or fried sheep thyroid or tablets of dried thyroid tissue.”

Quantitative determination of diazepam, nitrazepam and flunitrazepam in tablets using thin-layer chromatography–densitometry technique

A simple and reliable assay for diazepam, nitrazepam and flunitrazepam in tablets by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC)–densitometry is described. A quantity of a ground tablet mass, equal to the average weight of one tablet was sonicated in MeOH, mixed with appropriate internal standard, filtered and either injected directly into the liquid chromatograph, or after evaporation and reconstitution of an aliquot of the extract, was spotted on a silica gel thin-layer plate. A variable UV detector, operated at 254 nm was employed in both procedures. A C18, reversed phase 7 μm column was used for HPLC analysis; the mobile phase was a 1:1 (v/v) mixture of MeOH (40 °C) and 0.01 M phosphate buffer (pH 7, 80 °C). The TLC plate was developed in an unsaturated chromatographic chamber containing 100 ml chloroform–acetone (9:1); at room temperature, the mobile phase was allowed to travel 15 cm. The percentage of the active ingredient content of each tablet obtained by both procedures, was in the range of the stated amount except for one brand of diazepam tablets which contained ∼23% less active ingredient than the minimum prescribed amount. The TLC densitometry, although yields slightly higher values than the HPLC method, is preferred due to its simplicity, ease and low cost.

粉砕不可とされている錠剤・カプセル剤の調剤方法に関する検討

We examined the procedures for dispensing tablets or capsules that are not approved for crushing after checking the basis for such non-approval regarding 108 medicines introduced in our hospital. The problems are summarized as 1) a reduction in the pharmacological efficacy, 2) lowering the compliance due to a bitter taste or unpleasant odor, 3) dispersing hazardous powder, and 4) a disappearance of the efficacy of improved formulation such as for enteric coating.The taste of the ground tablets or capsules that are indicated to not be crushed was examined and compared with various concentrations of quinine hydrochloride powder in 8 healthy volunteers who showed a normal response to a bitter taste. Thirty-one out of 43 drugs were found to be tolerable to the taste, in which 13 drugs were less bitter than 0.5% quinine hydrochloride powder. However the other drugs either induced numbness or had a pungent taste and unpleasant odor, which were also considered to become the major reasons for nonapproval for crushing. Therefore, we found that several tablets have no serious problems, when they are dispensed after grinding. On the other hand, a number of hygroscopic medicines and anticancer agents tended to easily disintegrate in water. As a result, they can be prescribed by suspending them in water immediately before taking them. Our findings suggest that several tablets or capsules that are non-approved for crushing may thus be dispensed without any serious problems after crushing or disintegrating them in water. Therefore, our present findings may offer some useful information on the countermeasures for dispensing tablets and capsules that are not approved for crushing.

Physical stability and solubility of the thermotropic mesophase of fenoprofen calcium as pure drug and in a tablet formulation

The aim of this study was to investigate and compare the physical stability and solubility of the liquid crystalline form of fenoprofen calcium as pure drug and in a proprietary tablet formulation (Nalfon ®), and to investigate if a simple heat treatment of a proprietary tablet containing fenoprofen calcium may lead to a physically stable formulation with enhanced dissolution rate and apparent solubility. The liquid crystalline form of fenoprofen calcium (thermotropic mesophase) was prepared by heating the crystalline drug to 125 °C to remove the water of crystallisation. Differential scanning calorimetry investigation revealed an endothermic peak at 89 °C upon heating (liquid crystal formation) attributable to water loss from the crystalline dihydrate. The liquid crystalline order was maintained upon cooling. No interference of tablet excipients with the thermal behaviour of the drug in the tablet formulation was observed. The crystalline dihydrate and liquid crystalline forms of fenoprofen calcium could be differentiated by diffuse reflectance infra-red spectroscopy and X-ray powder diffraction, both as pure drug and in tablet formulation. The supercooled liquid crystal (thermotropic reversed hexagonal phase) alone and in preheated and ground tablets was physically stable when stored in a dry environment or at 33% relative humidities (RH) at both 20 and 40 °C for 2 months. At 40 °C and 75% RH the supercooled mesophase extensively converted to the crystalline dihydrate within 6 days. Liquid crystalline fenoprofen calcium stored at 20 °C and 75% RH showed only partial dihydrate conversion after 2 months of storage. The solubility of the crystalline dihydrate alone and from the tablet formulation was 2.8±0.2 mg/ml and 3.0±0.2 mg/ml (mean±s.d.), respectively, (not significantly different), whereas the maximum solubility of the liquid crystal was 5.0±0.3 mg/ml (mean±s.d.) and 6.9±0.6 mg/ml (mean±s.d.), respectively (significantly different). The difference in maximum solubility between the crystalline dihydrate form of fenoprofen calcium and the fenoprofen calcium mesophase was highly significant, for both the pure drugs and the tablet formulations. The dissolution rate of the liquid crystalline fenoprofen calcium in preheated, intact tablets was significantly lower than that of the crystalline form in non-preheated tablets. Gross visual changes and scanning electron microscopy indicated that the disintegration properties of the tablet may be detrimentally effected by heating the tablet to 125 °C, diminishing the beneficial effect of improved solubility of the liquid crystal. The study has shown that conversion of the crystalline form of fenoprofen calcium to the liquid crystal can enhance the apparent solubility of the pure drug and the drug in presence of tablet excipients, but that the conversion should be performed before tablet formulation in order to increase dissolution of this poorly water-soluble drug.

ザイボックス錠を粉砕して製した懸濁液の安定性に関する検討

Zyvox® (linezolid), an oxazolidinone-class synthetic antibacterial agent, has been approved for the treatment of vancomycin-resistant Enterococcus faecium infections. Although there are three forms of this drug, including injection, tablets and oral suspension, presently available overseas, only injection and tablets have so far been approved in Japan. It is possible to use ground tablets as an oral suspension. However, the quality including the stability of linezolid in such a suspension has not yet been studied. In this study, we therefore, examined the stability of linezolid in a suspension of ground tablets and the characteristics of such a suspension. The solubility of linezolid was low, and approximately 85% of linezolid was suspended in a solid phase. Linezolid was stable in the suspension, and there were no differences in the pH for up to 24 hours. However, precipitation occurred rapidly after the ground tablets had been suspended. The concentration of linezolid in the upper layer of the suspension decreased to half of the initial concentration in 15 min.In conclusion, Zyvox® was found to be stable and therefore is considered suitable to be ground and used in an oral suspension. Such suspensions should be re-suspended just before use, especially when the suspension is pre-constituted.

Simultaneous determination of melatonin and pyridoxine in tablets by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method for the qualitative and quantitative determination of melatonin plus pyridoxine commercial tablets is described. Melatonin and pyridoxine were simultaneously determined by GC-MS after extraction from ground tablets with methanol and derivatization with N-methyl-N-N-trimethlylsilyltrifluoroacetamide (MSTFA). The mass chromatograms were generated using 232 m/z ion for melatonin and 280 m/z ion for pyridoxine, respectively. Splitless injection offers good reproducibility with a standard deviation of 2%. The developed method was applied to analyze the melatonin and pyridoxine content from two different tablet formulations. Also, recovery, detection and quantification limits are reported.

Packed-column supercritical fluid chromatography for the analysis of isosorbide-5-mononitrate and related compounds in bulk substance and tablets

We describe a packed-column supercritical fluid chromatographic method that can be used for the analysis of isosorbide-5-mononitrate (5-ISMN) bulk substance and the 5-ISMN content of Imdur tablets. The method is based on methanol-modified carbon dioxide as the mobile phase and porous graphitized carbon (PGC, Hypercarb) as column support at 40°C and 100 bar back pressure. The method makes it possible to simultaneously determine 5-ISMN and related compounds. In order to elute NO 3 − with acceptable retention time a quarternary ammonium hydrogen sulfate salt is added to the methanol modifier. An almost linear increase of the retention time with increasing carbon content of the counter ion was found. Tetramethyl ammonium hydrogen sulfate 5 mM in methanol was used in the final method as polar modifier for the simultaneous determination of possible degradation products within 12 min. The present method can separate and detect related compounds such as isosorbide-2,5-dinitrate, isomannidemononitrate and isosorbide-2-mononitrate at the 0.1% (w/w) level as required by regulatory guidelines. Nitrate can be detected down to about 0.02% (w/w). Repeated analyses of ground tablet powder gave an assay precision for isosorbide-5-mononitrate of 1.4% (R.S.D., eight samples and two injections of each). For related substances at an area percent of 0.1 the precision was less than 10%.

Toxoplasma encephalitis: influence of the vehicle on the efficacy of different doses of 2',3'-dideoxyinosine in mice.

In this study we investigated the effect of the antiretroviral molecule 2',3'-dideoxyinosine (Videx) against cerebral cysts in a murine model of toxoplasmic encephalitis caused by a wild cystic strain of Toxoplasma gondii. The role of the vehicle was also studied. Three doses were used: 50, 100 and 150 mg/kg of body weight/day. The doses of 50 and 150 mg/kg were prepared by dissolving pure 2',3'-dideoxyinosine powder in Maalox suspension before gavaging the mice; the dose of 100 mg/kg was prepared by grinding tablets of Videx that were suspended in water. A decrease in the number of cysts and a morphological modification of them were noted from day 15 with the lowest dose. The most important decrease could be observed with the dose of 100 mg/kg/d. After 30 days of treatment with this dose, 65% of the cysts were destroyed compared to controls. For the doses of 50 and 150 mg/kg/d prepared with Maalox, 36% and 51% of the cysts were destroyed respectively. So ddI has an effect on the cerebral cysts of T. gondii even at a low dose. The galenic formulation influences its action since the doses prepared with Maalox were less efficient than those prepared from ground tablets.

Determination of benzodiazepine in tablets studied by thermal desorption gas chromatography

Thermal desorption gas chromatography (TDGC) was applied to the analysis of 13 kinds of tablets containing different benzodiazepines (BZDs). An aliquot of ground tablet sample (0.1–1 mg), weighed into a platinum sample cup, was placed in a furnace pyrolyzer where the sample was heated up to a suitable temperature (150–500°C) so that BZD was desorbed from the sample powder. The desorbed components of BZDs were immediately transferred into a separation column by a helium carrier gas without using any trapping techniques. The desorbed components were identified by TDGC-mass spectrometry. Among various BZDs, fludiazepam, nimetazepam and mexazolam in tablet samples were determined by the present method. Thus, the results obtained were in good agreement with the specified values. Correlation coefficients of the calibration lines for the three BZDs’ ranged from 0.997 to 0.999 for several micrograms to about 10 μg of the components. Relative standard deviations of this method were <4.1% for 4 or 5 runs.

Capillary GC-MS determination of melatonin in several pharmaceutical tablet formulations.

A simple capillary GC-MS method for the determination of melatonin from tablets is proposed. Melatonin (N-acetyl-5-methoxytryptamine) was determined by gas chromatography-mass spectrometry after extraction from ground tablets with ethyl acetate and derivatization with N-methyl-N-trimethylsilyl-heptafluorobutyramide (MTSHFBA). Splitless injection offers good reproducibility with a standard deviation of +/- 2%. The proposed method was applied to analyse the melatonin content from three different tablet formulations.

調剤工程および服用時の薬剤損失 ジゴキシン製剤をモデルにして

It is well known that the bioavailability of digoxin is dependent on the dosage forms and the ground tablets of digoxin are also more frequently ordered instead of the powdered form for prescriptions. In the present study, the weight loss of the drug, due to the dispensing process and adherence to either the package or the measuring cup, was studied. Three dosage forms of digoxin including ground tablets, powders and elixir, were used as the model forms. Simulative dispensing was carried out using the conventional methods.For ground tablets and powders, a 2 to 3% weight loss in the dispensing process, and a 7 to 8% weight loss due to adherence to the package were observed. In the case of the elixir, a 0.3 to 0.4% weight loss in the dispensing process, and a 1.3 to 1.4% weight loss due to adherence to the measuring cup and the plastic bottle was observed.We thus conclude that the elixir is the most suitable digoxin dosage form for children who have difficulty swallowing tablets due to its smaller weight loss.

Determination of Felodipine in Tablets Using Accelerated Solvent Extraction

A method for the content determination of felodipine from tablets using accelerated solvent extraction (ASE) was developed. Acetonitrile, methanol and a mixture of the two (2:1, v/v) were evaluated as the extraction solvents, at two different temperatures, 50°C and 100°C, for ground tablets. Acetonitrile gave the fastest extraction and methanol the slowest at both temperatures. No difference in extraction efficiency was observed between the two temperatures. To minimize sample handling, extraction of whole tablets was performed using the same parameters as for the ground tablets. 100°C gave higher recoveries than 50°C. However, quantitative recovery could not be achieved within an acceptable extraction time due to slow mass transfer in whole tablets. Hence, a different approach was used where tablets were crushed in a filter paper inside the extractor cell using a pair of flat pliers. This approach provided a straightforward way of transferring the entire tablet to the cell without losses. The final method was capable of extracting over 98% of felodipine within 15 minutes of static extraction at 50°C and 1500 psi, using acetonitrile as the solvent. No target analyte breakdown was observed at these conditions.