Caffeine increases the analgesic properties of acetaminophen and therefore it is reasonable to use both substances together in one drug form in stronger pain. Currently, there are no commercially available pharmaceutical combination products containing acetaminophen and caffeine, which is present as granules. The aim of the study was to obtain twelve different granules with these therapeutic substances and determine the effect of various excipients on the quality of the drug form. All the granules were made by wet granulation. Two types of binders were used: polyethylene glycol 6000 (PEG) and polyvinylpyrrolidone K30 (PVP) as well as different types of fillers. The physical properties of granules were assessed in accordance to the requirements of the European Pharmacopoeia 8th ed. The highest apparent density was found in preparations containing calcium hydrophosphate (0.609 g/mL) and the lowest - containing mannitol (0.353 g/mL) as a filler. The Hausner ratio of most prepared granules ranged from 1.05 to 1.11, while the compressibility index ranged from 4.59 to 10.48%. The evaluation of properties of individual granules helped to indicate formulation with good features, which perhaps will be a good alternative to currently available painkillers with caffeine and acetaminophen.

The purpose of this work was to determine the effect of starch hydrolysates (SH) on the physicochemical properties of suppositories. The study was conducted with suppositories with acetaminophen (AAP) a typical antipyretic analgesic, as model drug on lipophilic (cocoa butter) and hydrophilic base (polyethylene glycol 1500 + 400). The suppositories with and without the addition of SH were examined for physicochemical tests according to European Pharmacopoeia 8th edition (Ph. Eur.): the uniformity of mass of single-dose preparation test, the softening time determination of lipophilic suppositories test, the disintegration of suppositories test, and dissolution test with flow-through apparatus. The results confirm the possibility of using starch hydrolysates as a cheap and safe addition to modify physicochemical properties of suppositories.

It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine.

It is well known that drugs can directly react with excipients. In addition, excipients can be a source of impurities that either directly react with drugs or catalyze their degradation. Thus, binary mixtures of three diuretics, torasemide, furosemide and amiloride with different excipients, i.e. citric acid anhydrous, povidone K25 (PVP), magnesium stearate (Mg stearate), lactose, D-mannitol, glycine, calcium hydrogen phosphate anhydrous (CaHPO4) and starch, were examined to detect interactions. High temperature and humidity or UV/VIS irradiation were applied as stressing conditions. Differential scanning calorimetry (DSC), FT-IR and NIR were used to adequately collect information. In addition, chemometric assessments of NIR signals with principal component analysis (PCA) and ANOVA were applied.Between the excipients examined, lactose and starch did not show any interactions while citric acid, PVP, Mg stearate and glycine were peculiarly operative. Some of these interactions were shown without any stress, while others were caused or accelerated by high temperature and humidity, and less by UV/VIS light. Based on these results, potential mechanisms for the observed interactions were proposed Finally, we conclude that selection of appropriate excipients for torasemide, furosemide and amiloride is an important question to minimize their degradation processes, especially when new types of formulations are being manufactured.

Acetaminophen and caffeine, popular therapeutic substances used to relieve pain or alleviate the symptoms of cold. The aims of the study were the comparison of granules, in terms of dissolution rate and moreover the development of spectrophotometric method to the simultaneous determination of both active pharmaceutical ingredients (APIs) in granules. The granules were tested by two pharmacopoeial methods of dissolution for solid dosage forms, and the dissolution profiles for each formulation were compared. A method of simultaneous determination of two medicinal substances by the double calibration method using derivative spectrophotometry was used. Considering the dissolution process carried out in the paddle apparatus, it was shown that more than 80% of acetaminophen and caffeine were released from each of the preparations in a clearly shorter time than 10 minutes. Carrying out the basket test, substances dissolved gradually, much slower than in the paddle method. The time required to release 80% of both active substances from majority of tested preparations was from 30 to 45 minutes. Application of the first derivative spectrophotometric method allows simultaneous determination of acetaminophen and caffeine in the mixture, without the need to separate them first.