Estimation of the release profiles of multi-unit dose tablets of theophylline from the release profiles of their components

Purpose: The objective of this study is to investigate whether the drug release profile of a multi-unit dose form consisting of fast and slow release components can be predicted from the release profiles of their components by simple summation. Method: The fast release component consisted of conventional granules of theophylline made by wet massing the drug powder with starch mucilage (20w/v). The slow release component consisted of matrix granules of the drug made by triturating the drug powder with melted carnuba wax (i.e. melt granulation). Each type of granules was compressed to tablets of weight 100; 150 or 200mg. To form the multi-unit dosage tablets of drug content 300mg each; the conventional and matrix granules were mixed in the ratio 1:2; 1:1 and 2:1; and compressed. The tablets were subjected to dissolution test and from the experimental release curve the prompt release (mp) in the first 1h; the maximum release (m ) and the time to attain it (t ) were obtained. Result: For a given composition of the multi-unit dose tablets; the theoretical release curve was obtained by summation of the release from each component at the different time intervals. The mp values of the theoretically estimated release curves were generally higher; while their t values were generally shorter than the corresponding values for the experimental curves. Conclusion: The indication is that drug release from the multi-unit dose tablets was more retarded than could be theoretically estimated. Apparently; the two components interfere with each other's release

Effect of Grewia gum on the mechanical properties of Paracetamol tablet formulations

Grewia gum has been evaluated as a binder in paracetamol tablet formulations. Compressional properties of the formulations were analyzed using density measurements and the compression equations of Heckel and Kawakita as assessment parameters. Formulations containing Grewia gum as a binder show a slower onset and lower amount of plastic deformation than those containing PVP. The Db values for formulations containing Grewia gum; increased with increased concentration up to 4w/w. Formulations containing Grewia gum were also found to exhibit higher degree of packing than those containing PVP. Yield values for formulations containing Grewia gum was found to be at variance with the binder concentration. The values increased between 1 and 2w/w and decreased between 2 and 4w/w. A linear relationship was found to exist between N/C and N for formulations containing Grewia gum at all concentrations. Grewia gum was found to improve the fluidity of paracetamol granulation better than PVP. This study suggests that Grewia gum compares favorably with the standard binder PVP used hence could be a useful substitute binder in paracetamol tablet formulations

Comparative Quality Assessment and In Vitro Dissolution Profile of some Paracetamol Tablet Generics Marketed in Nigeria

Background: Studies have shown an increase in the usage of generic drug products from multiple sources. These generic drugs are expected to satisfy similar established standards as the original or innovator brands. Aim: To assess the standards and interchangeability of six common brands of paracetamol (acetaminophen) tablet generics marketed in Nigeria. Methods: The biopharmaceutical parameters; weight uniformity and assay of active ingredients were carried out according to established methods. The dissolution rates and disintegration times were determined in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. A variation of the concept of dissolution efficiency (DE); known as predicted availability equivalent (PAE); was used to predict the likely in vivo bioavailability. Results: All the brands complied with specifications for the weight uniformity; friability; disintegration time and assay of active ingredient tests. In the dissolution efficiency determination; all the brands released more in SGF than SIF. Conclusion: The study showed that all the six brands of paracetamol tablet tested are interchangeable with one another and thus could be prescribed one in place of the other. This would lead to the reduction in the cost of treatment; increased drug availability and an enhanced patients compliance in the use of acetaminophen tablets

Aspects of microbial contamination of tablets dispensed in hospitals and community pharmacies in Benin City, Nigeria

PURPOSE: A research was carried out to investigate the incidence of microflora in tablets dispensed from large container packages used in hospitals and community pharmacies. It was designed to provide baseline data on the common biodegrading microorganisms associated with tablets in retail containers and to highlight the health implications of such observations and roles for pharmacists in self medication phenomenon in Nigeria. METHODS: The protocol for the study involved structured selection of representative named tablets from some public hospitals and community pharmacies within Benin metropolis. Constitutive microorganisms were elaborated and enumerated using standard microbiological protocols. RESULTS: Our results showed that all the tablets sampled had some form of microbial growth. However; aerobic mesophilic bacteria and fungi observed were within standard numerical limits. It was additionally observed that ascorbic acid and folic acid tablets; particularly from the community pharmacies failed the exclusive criteria for Enterobactereacea and Staphylococci. Tablets from public hospitals in general have lower incidence of exclusive microbial contamination; compared with community pharmacies. CONCLUSION: Tablets packed in large containers in retail pharmacies in Benin City are often contaminated with microbial growth. This has possible adverse consequences for those who obtain drugs stored in large containers

Short Paper - Reclosure Efficiency of Plastic Container Used for Multidose Packaging of Moisture Sensitive Aspirin Tablets

This study was conducted to determine the suitability of packaging aspirin tablets in one thousand tablet packs that require reclosure after dispensing each dose. The reclosure efficiency of the push-fit type closure of a plastic container in preventing moisture entry was determined and compared to a control container. Aspirin tablets used in this study were shown to be susceptible to moisture degradation leading to significant losses of potency (p less than 0.05). Loose placement of closure on container allowed significant gain of moisture into the container (p less than 0.05) and this could lead to significant loss of potency of aspirin tablets. However; if the closure is properly pushed down to fit; the moisture gain is not significant (p greater than 0.05). It can; therefore; be concluded that the proper use of push-fit closures on containers for packaging aspirin tablets provides effective protection and the use of more expensive single unit strip packaging; for example; is therefore not necessary

Effect of Compression Force; Humidity and Disintegrant Concentration on the Disintegration and Dissolution of Directly Compressed Furosemide Tablets using Croscarmellose Sodium as Disintegrant

PURPOSE: The effect of compression force; relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicelr-tablets was studied. METHODS: Mixtures of furosemide (12.5 percent w/w); Ac-Di-Solr (0; 0.625 percent to 10 percent w/w) and Avicelr PH200 (qs to 100 percent w/w) were prepared in a Turbularmixer at 69 rpm for 10 min. Tablets were stored for 6 months under conditions similar to the four climatic zones recognized by ICH. Tablet hardness; disintegration time and dissolution were measured. RESULTS: At the same compression force; disintegration time decreased as the disintegrant concentration increased above 0.625 percent w/w but an increase in compression force resulted in increased tablet crushing strength and apparent density; both of which prolonged the disintegration time. This effect was less significant when the disintegrant concentration was above 1.25 percent. However; storage under high relative humidity conditions (mediterranean or subtropical; hot and humid climate) caused softening of tablets leading to the spontaneous disintegration of tablets containing high concentrations of Ac-Di-Solr . CONCLUSION: Fast disintegration of tablets within 1-2 min is a prerequisite for improving the dissolution of furosemide. This was attributed to an increase in the speed at which the maximum surface area of the sparingly water-soluble drug is exposed to the dissolution medium. Ac-Di-Solr was an efficient disintegrant for furosomide tablets at low concentrations of 1.25 percent -10 percent because it rapidly released the hydrophobic drug particles from tablets. However; tablets containing 10 percent disintegrant must be protected from atmospheric moisture because storage at 60-70 percent relative humidity led to softening of tablets

Effects of Interacting Variables on the Tensile Strength and the Release Properties of Paracetamol Tablets

"PURPOSE: The individual and interaction effects of nature of binder (N); concentration of binder (C) and the relative density (D) on the tensile strength and release properties of paracetamol tablets have been studied using a 23 factorial experimental design. METHODOLOGY: Khaya gum; which represented the ""low"" level; and polyvinylpyrrolidone (PVP); which represented the ""high"" level; was used as binding agent at concentrations of 0.5 percent and 4 percentw/w in a paracetamol tablet formulation. The tensile strength; which is a measure of the bond strength of tablets; and the release properties of the tablets-measured by the disintegration and the dissolution times; were used as assessment parameters. RESULTS: Changing the concentration of binder and the relative density of the tablets from ""low"" to ""high"" led to an increase in the tensile strength and the disintegration and dissolution times of the tablets. The ranking of the individual coefficient values for the formulations was D less than N less than C for T and C > N less than D for the disintegration and dissolution parameters while the ranking for the interaction effects was N -D > N -C less than C - D for T and t[50]; N -C > N - D C -D for DT and C -D less than N -C > N -D for t[90]. CONCLUSION: The results suggest that khaya gum could be useful as an alternative binding agent to produce tablets with particular tensile strength and drug release profiles and there was considerable interaction between the variables employed on the tablet properties."

Comparative Analysis of Eight Brands of Sulfadoxine-Pyrimethamine Tablets

PURPOSE : The aim of the present study is to investigate the physicochemical equivalence of eight brands of tablets containing sulfadoxine-pyrimethamine (antimalarial drug combination) sourced from different retail Pharmacy outlets in the Nigerian market. METHOD : The quality and physicochemical equivalence of eight different brands of sulfadoxine-pyrimethamine combination tablets were assessed. The assessment included the evaluation of uniformity of weight; friability; crushing strength; disintegration and dissolution tests as well as chemical assay of the tablets. RESULTS : All the eight brands of the tablets passed the British Pharmacopoeia (BP) standards for uniformity of weight; disintegration and crushing strength. Three of the eight brands failed the friability test. One of the brands did not comply with the standard assay of content of active ingredients while another brand did not comply with the USP specifications for dissolution test for sulfadoxine-pyrimethamine tablets. There were no significant differences in the amounts of pyrimethamine and sulfadoxine released from the different brands (P greater than 0.05). CONCLUSION: Only three brands (registered by NAFDAC) out of the eight brands of sulfadoxine-pyrimethamine tablets that were analysed passed all the BP quality specifications and were physically and chemically equivalent. This study highlights the need for constant market monitoring of new products to ascertain their equivalency to the innovator product