Assessment of physical properties of granules with paracetamol and caffeine

Abstract

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.

Comparative dissolution studies on granules with acetaminophen and caffeine using the basket and paddle methods with simultaneous spectrophotometric determination of active substances

“…The results obtained in the paddle method of the dissolution test were consistent to the results obtained in the disintegration test, due to similar conditions -lack of a mechanical barrier. Each of the series of granules disintegrated in a time much shorter than 10 minutes, which suggests that the dissolution of active substances also took place in a relatively short time [2]. However, in the diagrams showing dissolution profiles, larger differences between individual series are visible in the case of the basket test method (Fig.…”

“…The dependence of the dissolution process on the type of binder is more noticeable in the basket method. The acceleration of dissolution due to the replacement of PEG 6000 with PVP K 30 is probably due to the lower binding of the powder mixture by PVP K 30, which is also indicated by the shorter disintegration time of granulates containing this type of binder [2].…”

“…The dissolution profiles for each formulation were compared. In our previous paper, we described a method of preparing and testing the physical properties of granules containing acetaminophen and caffeine [2]. This current paper also presents a spectrophotometric method of simultaneous determination of two…”

“…Preparation of Granules. The granules were made by way of the wet granulation method, as described in our previous paper [2]. PEG 6000 was the binder in granules series 1-5 and PVP K30 had the same function in granules series 6-10 (Table 1).…”

Quantifying the effect of glidant on the compaction and tableting properties of paracetamol granules

“…The angle of repose for each formulation of granules was measured using the fixed funnel method [31]. About 20 g of granules was poured at an angle of 45 º through a funnel fixed at the height of 8 cm onto a flat surface forming a conical heap of powder.…”