Common Tablet Research Articles

Characterization of strain rate sensitivity in pharmaceutical materials using indentation creep analysis

Understanding how a material's response to stress changes as the stress is applied at different rates is important in predicting performance of pharmaceutical powders during tablet compression. Widely used methods for determining strain rate sensitivity (SRS) are empirically based and can often provide inconsistent or misleading results. Indentation creep data, collected during hardness tests on compacts formed from several common tableting excipients, were used to predict each material's relative sensitivity to changes in strain rate. Linear relationships between Ln(indentation hardness) and Ln(strain rate) were observed for all materials tested. The slope values taken from these relationships were compared to traditional strain rate sensitivity estimates based on in-die Heckel analysis. Overall, the results from the two methods were quite similar, but several advantages were evident in the creep data. The most notable advantage was the ability to characterize strain rate sensitivity derived from plastic behavior with little influence of elastic deformation. For example, two grades of corn starch had very similar creep behavior, but their yield pressures were affected very differently when the compaction rate was increased. This inconsistency was related to the difference in the viscoelastic recovery exhibited by these two materials. This new method promises to allow a better understanding of strain rate effects observed during tablet manufacturing.

Characterizing Compaction-Induced Thermodynamic Changes in a Common Pharmaceutical Excipient

Work, heat, and internal energy change values were measured during compression of a common pharmaceutical tablet excipient, anhydrous lactose, using a compression calorimeter. Heat of solution measurements were used independently to measure the energy change caused by compaction. Both the compression calorimeter and the heat of solution measurements showed an increase in anhydrous lactose's energy state as a result of the net compression and decompression process. Excellent agreement between the energy change measured by compression calorimetry (0.94 J/g) and the energy change measured by solution calorimetry (0.91 J/g) strongly supports the data and results generated by the compression calorimeter. Furthermore, specific volume and specific surface area measurements were used to investigate the nature of the measured energy increase. The results indicate that the vast majority of the stored energy is most likely associated with residual strain within the compacted particles.

Preparation of carteolol hydrochloride matrix sustained-release pellets and evaluation in vitro/in vivo

The aim of this study was to prepare carteolol hydrochloride matrix sustained-release pellets, and to compare its performance in vivo with carteolol common tablets. The formula was optimized according to the roundness and the release of pellets with single-factor, and orthogonal test. The carteolol hydrochloride matrix sustained-release pellets were got by extrusion-spheronisaion, while the release rate in vitro was determined by rotate basket method with UV detection. The carteolol hydrochloride sustained release property was studied in New Zealand white rabbits after oral administration. The optimized prescription is composed of carteolol hydrochloride 5.5 g, MCC 6.0 g, SA 26.3 g, EC 21.0 g, CMC-Na 1.2 g. Drug release property in vitro were as follows: the release time is over 12 h, the drug release behaviors follow the first order equation and the process of drug releasing is drug diffusion with frame erosion. The Cmax, Tmax and AUC(0→24) of the pellets were 2.58 ± 0.43 (mg/ml), 4.20 ± 0.87 (h) and 22.19 ± 4.23 (mg/ml h), respectively. The Cmax, Tmax and AUC(0→24) of the tablets were 3.75 ± 0.59 (mg/ml), 1.00 ± 0.72 (h) and 18.70 ± 3.75 (mg/ml h). The carteolol hydrochloride sustained-release pellets have reasonable formulation and simple preparation technology; the pellets acquired perfect sustained-release properties in vitro/in vivo. Key words: Carteolol hydrochloride, sustained-release, pellets, in vitro, in vivo, evaluation

Sensitive and selective spectrophotometric assay of rizatriptan benzoate in pharmaceuticals using three sulphonphthalein dyes

Three simple, rapid, selective and sensitive spectrophotometric methods are described for the determination of rizatriptan benzoate (RTB) in bulk drug and in tablets. The methods are based on the formation of intense yellow colored ion–pair complexes between RTB and sulphonphthalein acid dyes, namely, bromophenol blue (BPB), bromocresol purple (BCP), bromothymol blue (BTB) in chloroform medium. The colored products are measured at 425nm (RTB–BPB complex, RTB–BCP complex) and 420nm (RTB–BTB complex). The reactions were extremely rapid at room temperature and the absorbance values remained constant for 90min (methods A and B) and over 12h (method C). Beer’s law was obeyed in the concentration ranges of 0.8–16.0, 1.0–20.0 and 1.2–24μgml−1 with molar absorptivity values of 1.76×104, 1.96×104 and 1.63×104lmol−1cm−1 for BPB, BCP and BTB methods, respectively. The limits of quantification (LOQ) were 0.39, 0.34 and 0.27μgml−1 for BPB, BCP and BTB methods, respectively. Other method validation parameters, such as precision, accuracy, robustness, ruggedness and selectivity, were satisfactory. The composition of the ion–pair was found to be 1:1 by Job’s method. The proposed methods were successfully applied to the determination of RTB in commercial tablets. No interference was observed from common tablet adjuvants. Statistical comparison of the results with the reference method showed excellent agreement and indicated no significant difference in accuracy and precision.

Titrimetric assay of lisinopril in aqueous and non-aqueous media

Four simple titrimetric procedures are described for the determination of lisinopril (LNP) in bulk and in pharmaceuticals based on the neutralization of basic-amino and acidic carboxylic acid groups present in LNP. Method A is based on the neutralization of basic amino groups using perchloric acid as titrant in anhydrous acetic acid medium. Method B, method C and method D are based on neutralization of carboxylic acid group using NaOH, sodium methoxide and methanolic KOH, as titrants, respectively. Method A is applicable over 2.0-20.0 mg range and the calculations are based in the molar ratio of 1:2 (LNP:HClO4). Method B, method C and method D are applicable over 2.0-20.0 mg, 1.0-10.0 mg and 5.0-15.0 mg range, respectively, and their respective molar ratios are 1:1 (LNP:NaOH), 1:2 (LNP:CH3ONa) and 1:1 (LNP:KOH). Intraday and inter day accuracy and precision of the methods were evaluated and the results showed intra- and inter-day precision less than 2.7% (RSD), and accuracy of < 2.5% (RE). The developed methods were applied to determine LNP in tablets and the results were validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test.

Fast and direct recognition of the active ingredients in tablets using hot cell membrane inlet mass spectrometry

This paper demonstrates that the active ingredient in many common tablets (anti-depressives, pain relievers, epileptic medicine and anti-histamines) can be recognized directly and without any pretreatment using hot cell membrane inlet mass spectrometry (hot cell MIMS). The tablets were simply placed in a sample vial and then dumped into a small oven heated to approximately 200 °C (the hot cell). The hot cell was interfaced directly to the ion source of an electron ionization mass spectrometer (EI-MS) via a polymer membrane. A few minutes thereafter an EI-MS spectrum of the chemicals desorped from the sample was recorded. Even though the tablets contained a significant number of chemicals (fillers) and often a polymer coating in addition to the active ingredients simple EI-MS spectra were recorded, wherefrom the active ingredient could be recognized by comparison with a standard EI-MS database. Of the eight tablets tested only one tablet, Bio-Melatonin (sleeping disorder), did not give a recognizable EI-MS spectrum. Over a period of 6 months the spectra recorded from the tablets did not change and the active ingredients were always recognized. The reproducibility of signal intensities from characteristic ions following successive injections was high (≈7%) for tablets without surface coating, whereas it varied up to 25% for tablets with a surface coating. Since hot cell MIMS is fully compatible with field portable instruments our results open the possibility of creating a small portable mass spectrometer for use in paramedical vehicles for immediate, on-site identification of medications found near intoxicated patients.

Setting the bar for powder flow properties in successful high speed tableting

Abstract An inadequate powder flow leads to problems in tablet manufacturing. The knowledge of minimum flow properties required for successful tableting on a high speed press is critically important to the efficient development of pharmaceutical tablets. This may be achieved by identifying a powder that exhibits minimally acceptable flow properties on a high speed tablet press. A grade of a common tablet excipient, microcrystalline cellulose (Avicel PH102) lies near the borderline between acceptable and poor flow regions during high speed tableting. It can therefore serve as a reference material for judging adequacy of flow properties of prototype formulations by the way of comparison. A powder exhibiting poorer flow properties than Avicel PH102 likely exhibits flow problems and should be avoided. An implementation of this simple approach in formulation development can minimize potential flow problems during large scale tablet manufacture.

Titrimetric assay of lisinopril in aqueous and non-aqueous media

Four simple titrimetric procedures are described for the determination of lisinopril (LNP) in bulk and in pharmaceuticals based on the neutralization of basic-amino and acidic carboxylic acid groups present in LNP. Method A is based on the neutralization of basic amino groups using perchloric acid as titrant in anhydrous acetic acid medium. Method B, method C and method D are based on neutralization of carboxylic acid group using NaOH, sodium methoxide and methanolic KOH, as titrants, respectively. Method A is applicable over 2.0-20.0 mg range and the calculations are based in the molar ratio of 1:2 (LNP:HClO4). Method B, method C and method D are applicable over 2.0-20.0 mg, 1.0-10.0 mg and 5.0-15.0 mg range, respectively, and their respective molar ratios are 1:1 (LNP:NaOH), 1:2 (LNP:CH3ONa) and 1:1 (LNP:KOH). Intraday and inter day accuracy and precision of the methods were evaluated and the results showed intra- and inter-day precision less than 2.7% (RSD), and accuracy of < 2.5% (RE). The developed methods were applied to determine LNP in tablets and the results were validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test. The accuracy was further ascertained by recovery studies via standard addition technique. No interferences from common tablet exipients was observed.

Accelerated degradation of ibuprofen in tablets

The forced degradation of 11 ibuprofen tablet brands was carried out according to current industry best practices. The results indicated an incompatibility between ibuprofen and two common tablet excipients (polyethylene glycol and polysorbate 80) that were observed to accelerate the degradation of ibuprofen in tablets stored for three weeks at 70°C/75% RH. Studies of binary drug/excipient samples supported the conclusion. One degradant that was observed at increased levels was 4-isobutylacetophenone (4-IBAP), which is a known toxin.

Bromatometric assay of simvastatin in pharmaceuticals

Titrimetric and spectrophotometric methods are proposed for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods employ bromate-bromide mixture in acid medium as the brominating agent and iron (III) and thiocyanate as auxiliary regents. In titrimetry, SMT is treated with a measured excess of bromate-bromide mixture in HCl medium, and after a definite time, the unreacted bromine is determined iodometrically. In spectrophotometric method, the residual bromine is reduced by iron (II) and the resulting iron (III) is complexed with thiocyanate, and the absorbance is measured at 470 nm. In both methods, the amount of in situ generated bromine corresponds to the SMT content. The experimental conditions are optimized. Titrimetry is applicable over 1–10 mg range and the calculations are based on the molar ratio of 1: 0.666 (SMT: KBrO3). In spectrophotometric method, Beer’s law is obeyed over the concentration range 1–10 µg/mL. The calculated molar absorptivity is 3.02 × 104 L/mol cm and the corresponding sandel sensitivity being 0.0081 µg/cm2. The limit of detection (LOD) and limit of quantification (LOQ) are calculated to be 0.10 and 0.31 µg/mL, respectively. The intra-day and inter-day precision calculated from the analysis of pure SMT were less than 2 and 2.7%, respectively. The methods were satisfactorily applied to the determination of SMT in tablets, and no interferences from common tablet excipients were observed. The validity of the methods was further ascertained by parallel assay by an established technique and by recovery studies.

Spectrophotometric Determination of Pantoprazole Sodium in Pharmaceuticals Using N-Bromosuccinimide, Methyl Orange and Indigo Carmine as Reagents

Two sensitive spectrophotometric methods are presented for the assay of pantoprazole sodium sesqui hydrate (PNT) in bulk drug and in formulations using N-bromosuccinimide (NBS) and two dyes, methyl orange and indigo carmine, as reagents. The methods involve the addition of a known excess of NBS to PNT in acid medium, followed by determination of unreacted oxidant by reacting with a fixed amount of either methyl orange and measuring the absorbance at 520 nm (method A) or indigo carmine and measuring the absorbance at 610 nm (method B). In both methods, the amount of NBS reacted corresponds to the amount of PNT and the measured absorbance is found to increase linearly with the concentration of PNT which is corroborated by the correlation coefficients of 0.9959 and 0.9985 for method A and method B, respectively. The systems obey Beer's law for 0.1 - 2.0 mu g mL(-1) and 0.5 - 6.0 mu g mL(-1) for method A and method B, respectively. The limits of detection and quantification are also reported for both methods. Intra-day and inter-day precision,. and accuracy of the methods have been evaluated The methods were successfully applied to the assay of PNT in tablet preparations and the results were statistically compared with those of the reference method by applying Student's t-test and F-test. No interference was observed from the common tablet excipients. The accuracy of the methods was further ascertained by performing recovery studies via standard-addition method.

Use of chloramine-T and two dyes in the sensitive determination of stavudine in pharmaceuticals

Three new methods are described for the assay of stavudine (STV) in bulk drug and in dosage forms using chloramine-T (CAT) and two dyes, methyl orange and indigocarmine, as reagents. Titrimetry involves treating STV with a measured excess of CAT in hydrochloric acid medium, and after the oxidation of STV is judged to be complete, the unreacted oxidant is determined iodometrically. Spectrophotometric methods entail the addition of a known excess of CAT to STV in hydrochloric acid medium followed by determination of residual oxidant by reacting with a fixed amount of either methyl orange and measuring the absorbance at 520 nm (Method A) or indigo carmine and measuring the absorbance at 610 nm (Method B). In all the methods, the amount of CAT reacted corresponds to the amount of STV. In titrimetric method, the reaction follows 1:1 stoichiometry (STV: CAT), and is applicable over the range 1.5-10 mg of STV. In spectrophotometric methods, the absorbance is found to increase linearly with concentration of STV. The systems obey Beer's law for 0.2-2.0 and 1.0-10.0 mg/mL for method A and method B, respectively. The apparent molar absorptivities are calculated to be 5.7x10(4) and 1.5x10(4) L/mol/cm for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.004 and 0.015 µg/cm². The limits of detection and quantification are reported for both methods. Intra-day and inter-day precision and accuracy of the developed methods were evaluated as per the current ICH guidelines. The methods were successfully applied to the assay of STV in tablet and capsule formulations and the results were compared with those of a reference method by applying Student's t-test and F-test. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by performing recovery experiments via standard-addition method.

Rapid titrimetric and spectrophotometric assay methods for the determination of lamivudine in pharmaceuticals using iodate and two dyes

One titrimetric and two spectrophotometric methods, which are simple, sensitive and rapid, are described for the assay of lamivudine in bulk drug and in tablet dosage forms using potassium iodate and two dyes, methyl orange and indigocarmine, as reagents. In titrimetry, an aqueous solution of lamivudine is titrated directly with iodate in an acidic medium, and in the presence of an excess of bromide using methyl orange as an indicator. After the decoloration of the red color of methyl orange, the residual bromine is titrated iodometrically to a starch endpoint. Spectrophotometric methods involve the addition of a known excess of iodate in an acidic medium and in the presence of an excess of bromide followed by the determination of residual bromine by the reaction with a fixed amount of either methyl orange and measuring the absorbance at 520 nm (method A), or indigo carmine and measuring the absorbance at 610 nm (method B). In all methods, the amount of iodate which reacted corresponds to the amount of lamivudine content. The titrimetric method is applicable over the 1.5–8.0 mg range. The systems obey Beer’s law for 0.5–5.0 µg/mL (method A) and 1.25–12.5 μg/mL (method B). The calculated apparent molar absorptivity values are found to be 3.3 × 104 and 9.3 × 103 L mol−1 cm−1, for method A and method B, respectively, and the corresponding Sandell sensitivity values are 6.94 and 24.62 ng/cm2. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-and interday precision and accuracy for the developed methods have been evaluated. The methods were successfully applied to the assay of lamivudine in tablet form and the results were compared with those of a reference method by applying the Student’s t-test and F-test. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments using the standard addition technique.

Rapid titrimetric and spectrophotometric methods for salbutamol sulphate in pharmaceuticals using N-bromosuccinimide

One titrimetric and two spectrophotometric methods which are simple, sensitive and rapid are described for the assay of salbutamol sulphate (SBS) in bulk drug and in tablet dosage forms using N-bromosuccinimide (NBS) and two dyes, rhodamine-B and methylene blue, as reagents. In titrimetry, aqueous solution of salbutamol sulphate is treated with a measured excess of NBS in acetic acid medium and after the oxidation of SBS is complete, the unreacted oxidant is determined iodometrically. Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual oxidant by reacting with a fixed amount of either rhodamine B and measuring the absorbance at 555 nm (method A) or methylene blue and measuring the absorbance at 665 nm (method B). In all methods, the amount of NBS reacting corresponds to the amount of SBS content. Titrimetric method is applicable over 1.74 x 10(-4) - 8.68 x 10(-4) mol L(-1) range and the reaction stoichiometry is found to be 1:6 (SBS:NBS). In spectrophotometric methods, the absorbance is found to increase linearly with the concentration of SBS, which is corroborated by the correlation of coefficients of 0.9993 and 0.9988 for method A and method B, respectively. The systems obey Beer's law for 0.25-1.75 microg mL(-1) (method A) and 0.5-5.0 microg mL(-1) (method B). The calculated apparent molar absorptivity values were found to be 2.10 x 10(5) and 6.16 x 10(4) L mol(-1) cm(-1), for method A and method B, respectively. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-day and inter-day precision and accuracy for the developed methods were evaluated. The methods were successfully applied to the assay of SBS in tablet and capsule formulations and the results were statistically compared with those of a reference method. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via the standard-addition technique.

Studies on Bi-Layer Osmotic Pump Tablets of Water-Insoluble Allopurinol with Large Dose: In Vitro and In Vivo

Controlled release bi-layer osmotic pump tablets (BOPT) of water—insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro–in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use.

SubcriticalWater Extraction and Determination of Nifedipine in Pharmaceutical Formulations

A rapid and simple continuous method for the extraction of nifedipine from tablets was developed by using pressurized hot water at 150 degrees C. This is the first time that subcritical water was applied to the extraction of low-polarity compounds in pharmaceutical analysis. The method is based on the increment in solubility of nifedipine in subcritical water. Extraction temperature and static and dynamic extraction time were optimized in order to reach quantitative extraction of the drug from the tablets. After extraction, the drug was determined by spectrophotometry by measuring absorbance at 338 nm. Accuracy and precision of the method were determined by analysis of 10 synthetic samples of pharmaceutical formulations prepared with common tablet excipients. Recovery was found to be 99.2% with a relative standard deviation of 1.9%, which indicates that the excipients of the formulation do not interfere in the determination. The method was applied to the determination of the drug content uniformity in tablets.

New Sensitive Spectrophotometric Methods for the Determination of Raloxifene Hydrochloride in Pharmaceuticals Using Bromate‐Bromide,Methyl Orange and Indigo Carmine

Two new sensitive spectrophotometric methods are proposed for the determination of raloxifene hydrochloride (RLX) using bromate‐bromide mixture and two dyes, methyl orange and indigocarmine, as reagents. The methods entail the addition of a known excess of bromate‐bromide mixture to RLX in hydrochloric acid medium followed by determination of residual bromine by reacting with a fixed amount of either methyl orange and measuring the absorbance at 520 nm (Method A) or indigo carmine and measuring the absorbance at 610 nm (Method B). In both methods, the amount of bromine reacted corresponds to the amount of RLX. The absorbance is found to increase linearly with concentration of RLX. Under the optimum conditions, RLX could be assayed in the concentration range 0.1‐2.0 and 0.5‐6.0 μg mL-1 by method A and method B, respectively. The apparent molar absorptivities are calculated to be 1.9×105 and 4.5×104 L mol-1cm-1 for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.003 and 0.011 μg cm-2. The limits of detection and quantification are also reported for both methods. Intra‐day and inter‐day precision and accuracy of the developed methods were evaluated as per the current ICH guidelines. The methods were successfully applied to the assay of RLX in its tablet formulation and the results were compared with those of a reference method by calculating the Student’s t‐value and F‐value. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via standard‐addition procedure.

Flow-through Chloroquine Sensor and Its Applications in Pharmaceutical Analysis

Poly (vinyl chloride) membrane electrodes that responded selectively towards the antimalarial drug chloroquine are described. The electrodes were based on the use of the lipophilic potassium tetrakis(4-chlorophenyl)borate as ion-exchanger and bis(2-ethylhexyl)adipate (BEHA), or trioctylphosphate (TOP) or dioctylphenylphosphonate (DOPP) as plasticizing solvent mediator. All electrodes produced good quality characteristics such as Nernstian- and rapid responses, and are minimally interfered with by the alkali and alkaline earth metal ions tested. The membranes were next applied to a flow-through device, enabling it to function as flow-injection analysis (FIA) detector. The performance of the sensor after undergoing the FIA optimization was further evaluated for its selectivity characteristics and lifetime. Results for the determination of chloroquine in synthetic samples that contained common tablet excipients such as glucose, starch, and cellulose, and other foreign species such as cations, citric acid or lactic acid were generally satisfactory. The sensor was also successfully used for the determination of the active ingredients in mock tablets, synthetic fluids and biological fluids. The sensor was applied for the determination of active ingredients and the dissolution profile of commercial tablets was also established.

Spectrophotometric Methods for the Determination of the Antidepressant Drug Paroxetine Hydrochloride in Tablets

Simple, sensitive, and accurate visible spectrophotometric methods are described for the determination of paroxetine hydrochloride (PA) in tablets. Among them, the first 3 methods are based on the ion-pair complexes of PA formed with bromothymol blue (BTB), bromophenol blue (BPB), and bromocresol green (BCG) in aqueous acidic buffers. The complex species extracted into chloroform were quantitatively measured at 414 nm with BTB and BCG and at 412 nm with BPB. Beer's law was obeyed over the concentration ranges of 2-20, 2-16, and 2-16 microg/mL, respectively. The fourth method described is based on a coupling reaction between PA and 7-chloro-4-nitrobenzofurazon (NBD-Cl) in borate buffer, pH 8.5, in which a yellow reaction product that was measured at 478 nm was formed. The Beer's law range for this method was 2-10 microg/mL. The last method developed describes the interaction of PA base, as an n-electron donor, with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as a pi-acceptor, in acetonitrile to give blue-colored TCNQ- radical anion with absorption maxima at 750 and 845 nm. Measured at 845 nm, the absorbance-concentration plot was rectilinear over the range of 1.5-15 microg/mL. The new methods developed were successfully applied to the determination of PA in tablets without any interference from common tablet excipients. The results of the methods were in good agreement with those obtained with an official liquid chromatographic method. This report describes first colorimetric methods for the determination of PA.

Variability in Tablet Fragment Weights When Splitting Unscored Cyclobenzaprine 10 mg Tablets

To determine the weight variation and calculated dosing variability of tablet fragments upon splitting unscored cyclobenzaprine hydrochloride 10 mg tablets using two common tablet splitting devices. Comparative pharmaceutics study. Pharmacy school laboratory. Not applicable. Unscored cyclobenzaprine hydrochloride 10 mg tablets from one generic manufacturer were split with a tablet splitter or a kitchen knife by a licensed pharmacist and two doctor of pharmacy students (n = 15 tablets for each method per participant). Fragment weights (FWs) were compared with the theoretical weights (TWs), which were calculated as one half of the mean weight of the tablets used in each part of the experiment; means, relative standard deviations (RSDs), and percentages of TW were also calculated. The mean weight before splitting the 45 tablets with the tablet splitter was 136.6 +/- 2.1 mg (TW = 68.3 mg). The mean FW after splitting was 67.9 +/- 7.9 mg. The RSD of 11.6% corresponded to a range of 69.4% to 130.2% of the TW and an estimated drug content of the split fragments between 3.47 mg and 6.51 mg. The mean weight before splitting the 45 tablets cut with a kitchen knife was 136.6 +/- 2.0 mg (TW = 68.3 mg). The mean FW was 68.0 +/- 15.7 mg with a RSD of 23.2%, corresponding to a range of 49.9% to 149.5% of the TW and an estimated drug content of the split fragments between 2.49 mg and 7.48 Tablet fragments obtained after splitting this generic cyclobenzaprine 10 mg product varied considerably in weight and estimated drug content. Accordingly, splitting cyclobenzaprine 10 mg tablets to achieve 5 mg doses could result in unpredictable dosing and therapeutic response.