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.

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.

A simple, rapid, accurate and precise spectrophotometric method for simultaneous estimation of diclofenac sodium and papaverine hydrochloride in combined tablet and the dissolution media used in the release studies has been developed. It employs formation and solving of simultaneous equation using two analytical wavelengths corresponding to diclofenac sodium and papaverine hydrochloride in the dissolution medium. This method obeys Beer’s Law in the employed concentration ranges of 2.5-25 µg/mL for two active substances. The method was validated.

Four formulas of granules with caffeine were chosen to examine the influence of excipients on dissolution profiles of active substance from this drug form. The formula I: caffeine 1.0 parts, potato starch 69,3 parts, lactose 29,7 parts, glycerol 86% 2.0 parts, gelatin mucilage 4% (w/w) 98.0 parts; the formula II: caffeine 1.0 parts, Avicel 49,5 parts, lactose 49,5 parts, glycerol 86% 2.0 parts, gelatin mucilage 4% (w/w) 98.0 parts; the formula III: caffeine 1.0 parts, D-Mannitol 99,0 parts, glycerol 86% 2.0 parts, gelatin mucilage 4% (w/w) 98.0 parts and the formula IV: caffeine 1.0 parts, Avicel 49,5 parts, lactose 49,5 parts, and 0.5% solution of PVP 100.0 parts. This solution was prepared by dissolution of 0.5 parts PVP in 95.5 parts of mixture of ethanol 96° and water 1:1 (w/w). The granules were obtained in wet granulator. Their flow properties, moisture content, disintegration time and dissolution of active substance were tested. All granules passed the pharmacopoeial dissolution test because 80% of caffeine dissolved in 10 minutes time.