Release Characteristics of Diltiazem Hydrochloride Wax-Matrix Granules – Thermal Sintering Effect

The aim of this study was to investigate the release characteristics of matrix (non-disintegrating) granules consisting of diltiazem hydrochloride (model drug) and glyceryl behenate (a wax matrix forming polymer)for sustained release application using sintering technique. The granules of diltiazem hydrochloride-wax matrix were prepared by melt granulation technique. This was formed by triturating the drug powder with a melted glyceryl behenate (drug: wax ratio, 3:1). The granules were subsequently sintered at 60 and 700C for 1, 1.5 and 3h. The unsintered and sintered wax matrix granules of diltiazem hydrochloride were evaluated for physicochemical parameters and in vitro dissolution studies. The dissolution data were subjected to analysis using different mathematical models namely – zero order flux, first order, Higuchi square root of time, then Korsmeyer and Peppas model. Fourier-Transform Infrared Spectroscopy (FTIR) was carried out to investigate any chemical interactions between the drug and the added recipients before and after sintering. There was increased drug release retardation of diltiazem hydrochloride-wax matrix granules with sintering. The retardation depended on the temperature and duration of sintering. For instance, formulations sintered at 60 and 70°C for a period of 1.5h gave maximum release (m), time to attain maximum release (t) and dissolution rate (m/t) of 96.1%, 95.2%, 5h, 9h, 19.2%h-1 and 10.6%h-1 respectively. The drug release was by Higuchi controlled diffusion mechanism and it followed Fickain diffusion mechanism (

Effect of matrix granulation and wax coating on the dissolution rates of paracetamol granules

The study was carried out to investigate the release profile of matrix (non-disintegrating) granules consisting of paracetamol (drug) and acrylatemethacrylate copolymer, a matrix forming material. Theeffect of coating the matrix granules with wax on the drug release profiles was also investigated. The objective was to produce drug particles of different release profiles for application as multi-unit dosageforms. The matrix granules were formed by massing paracetamol powder with a concentrated ethanolic solution of the acrylatemethacrylate copolymer (40%, w/v) followed by drying and screening. Waxcoating was achieved by mixing the matrix granules with a melt of carnuba wax. Conventional granules of paracetamol were made by granulation with starch mucilage (20%, w/v); this served as reference samples for comparison. The granules were subjected to size analysis, packing/flow property, friability and dissolution tests. All the granules (i.e. conventional, matrix as well as the coated matrix granules) flowed readily and were also compressible upon tapping. The compressibility index values wereconventional granules (39±2.2%), matrix granules (27±1.8%) and coated matrix granules (24±1.9%). The friability values were conventional granules (1.96±0.02), matrix granules (0.78±0.01) and coated matrixgranules (0.63±0.03), indicating that matrix granulation increased the cohesive strength of the granules. The dissolution rates were conventional granules (16% h-1), matrix granules (9.4% h-1) and coated matrixgranules (4.4% h-1). Thus, matrix granulation and wax coating of the matrix granules are approaches for retarding drug release and hence prolonging the biologic action of drugs with short biologic half liv

Modeling of drug release from multi-unit dosage tablets of theophylline

A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release dose (400 mg) to be releasedover 11 h at a first order release rate constant of 0.24 h-1. The prompt release component (A) consisted of conventional granules of the drug while the sustained release component (B) was made up of matrixgranules of the drug obtained by melt granulation i.e. granulating the drug powder with a melted wax (carnuba). To form the multi-unit dose tablets, granules of A and B were mixed together in variousproportions in the ratios (A: B) 2:1, 1:1 and 1:2. The disintegration times of the tablets and their dissolution profiles were measured to investigate consistence with the model. The results showed thatthe tablets generally disintegrated readily within 10 min irrespective of the proportion of A to B. Of the various formulations tested, only the formulation consisting of A and B in the ratio 1:1 gave dissolutionprofile that was comparable to that of the model. The following were the dissolution parameters of this formulation: the maximum release (m) = 580 mg, prompt release dose (mp) = 180 mg, time to attainmaximum release (t) = 11 h and first order release rate constant (k1) = 0.27 h-1 which is comparable with the release data for the model. The other formulations deviated by giving mp and t that were either toohigh or too low compared with those of the model. The indication is that the prompt release dose was not determined only by the amount of A in the multi-unit dose formulation but also by the amount of B,attributable to the deformation of granules of A into B during tableting

In-vitro Characterization of Optimized Multi-Unit Dosage Forms of Theophylline and its Solid State Characterisation

The objective of this study is to compare the drug release profile of an optimized multi-unit dose (MU) tablet consisting of rapid and slow release components, a formulated sustained released tablet and two brands of sustained release tablet formulations in the market with a designed model. The fast release component consisted of conventional granules while the slow release component consisted of wax granules of theophylline. The optimized MU tablets was formed by mixing the conventional and matrix granules in ratio 1:1 and compressed. Parameters evaluated were tablet tensile strength and dissolution studies. The optimized formulation was characterized with Differential Scanning Calorimetry and Fourier-Transform Infrared Spectroscopy. Results showed that the optimized MU tablets gave dissolution profile that was comparable with that of the designed model. The following were the dissolution parameters of the optimized MU formulation: the maximum release (m∞) = 91%, prompt release dose (mp) = 24%, time to attain maximum release (t∞) = 12h and first order release rate constant (k) = 0.20 h-1 which is comparable with the release data for the model. The other formulations deviated by giving mp and t∞ that were too low compared with those of the model. There were also no drug/excipient interactions. The indication is that the prompt release dose was determined not only by the amount of the rapid release components in the MU dose formulation but also by the amount of sustained release components, attributable to the deformation of granules of rapid components into that of slow release components during tablet formulation.Keywords: Multiunit dose tablet, theophylline, Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR)J. Appl. Sci. Environ. Manage. Dec, 2011, Vol. 15 (4) 649 - 65

Current trends in the production and biomedical applications of liposomes: a review

A review of literature was carried out to determine methods of production of liposomes, their stability, biodistribution and their uses as drug delivery systems. The conventional method of preparing liposomes is basically for the multilamellar vesicles (MLVs). However, other methods are used to reduce the size of these MLVs to small unilamellar vesicles (SUVs) so as to increase their plasma lifetime and consequently increase the possibility of achieving greater tissue localisation. Some of these methods of size reduction are sonication and high pressure extrusion. Each of these methods has its own advantages and disadvantages. Large unilamellar vesicles (LUVs), on the other hand, are prepared mainly by detergent removal method and reverse phase extrusion technique. There are also improved pharmacokinetic properties with liposomal drugs compared to free drugs, though some formulation factors affect the release kinetics of the liposomal drugs. The review also shows that liposomes have a lot of biomedical applications and uses. They have been used in drug targeting, oral delivery of vaccines, insulins, peptides and some compounds, which are usually degraded in the gastrointestinal tract. It has also found application in topical therapy especially in the eye and lungs. Other areas of application are in cancer chemotherapy and treatment of human immunovirus (HIV) infection. The control of the stability of liposomes is an essential pre-requisite for effective use as drug carriers. Leakage of the liposome is attributable mainly to differences in lamellar structure. For instance, MLVs are less prone to leakage than ULVs. The use of a combination of saturated phospholipid and cholesterol in the formulation of the liposomes has also been found to enhance stability with lower tendency to leakage

Influence of some starch binders on the brittle fracture tendency of paracetamol tablets

The study was carried out to compare the binder effects of cassava and cocoyam starch with that of maize starch BP. The parameters investigated were the brittle fracture index (BFI), the tablet packingfraction (Pf), and tensile strength (T). Mucilages of the starches of varying concentrations; 15, 20, and 25% (w/v) were formed; their viscosities were determined and used to form paracetamol granules bywet-massing. The granules were compressed at different compression loads (arbitrary units on the load scale; 8, 9 and 9.5). At all given compression loads and at all binder concentration, cassava starchmucilages binder produced the hardest and most compact tablets with the least tendency to brittle fracture compared with cocoyam or maize starch mucilage. For instance, the BFI values at the compression load, 8 were 0.13 (tablets formed with cassava starch mucilage 20% w/v) 0.18 (tablets formed with cocoyam starch mucilage 20% w/v) and 0.35 (tablets formed with maize starch mucilage 20% w/v). Increase in compression load (8 to 9.5) increased the BFI of these tablets while an increase in binder concentration generally caused a decrease in BFI of these tablets. This decrease was less marked at higher compression load. The results indicate that cassava starch mucilage which was themost viscous, displayed the highest potential for ameliorating brittle fracture during manufacture of paracetamol tablets

Photosensitive drugs: a review on their photoprotection by liposomes and cyclodextrins.

Nowadays, an exciting challenge in the drug chemistry and technology research is represented by the development of methods aimed to protect molecular integrity and therapeutic activity of drugs from effects of light. The photostability characterization is ruled by ICH (The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which releases details throughout basic protocols of stability tests to be performed on new medicinal products for human use. The definition of suitable photoprotective systems is fundamental for pharmaceutical manufacturing and for human healthy as well, since light exposure may affect either drugs or drug formulations giving rise even to allergenic or mutagenic by-products. Here, we summarize and discuss the recent studies on the formulation of photosensitive drugs into supramolecular systems, capable of entrapping the molecules in a hollow of their structure by weak noncovalent interactions and protecting them from light. The best known supramolecular matrices belong to the 'auto-assembled' structures, of which liposomes are the most representative, and the 'host-guest' systems, of which cyclodextrins represent the most common 'host' counterpart. A relevant number of papers concerning the use of both liposomes and cyclodextrins as photoprotection systems for drugs has been published over the last 20 years, demonstrating that this topic captures interest in an increasing number of researchers

Influence of non ionic surfactants on the release characteristic of wax-matrix ibuprofen granules formed by thermal technique

This study was carried out to investigate the influence of non ionic surfactants (polysorbate 80 or sorbitan monooleate) on the release characteristics of wax-ibuprofen matrix granules. Ibuprofen-wax matrix granules were prepared by melt granulation technique. This was formed by triturating ibuprofen powder (100 g) with 20 g of carnauba wax with varying concentrations of non ionic surfactant i.e. polysorate 80 or sorbitan monooleate (0-10 %w/w), and then screened through sieves. The content of carnuaba wax in each formulation was 16.7 %w/w. The granules were evaluated for flow and packing properties. The formed granules were then encapsulated and the in vitro dissolution profile, release kinetics and mechanism were studied. The tap and bulk densities were not affected by the presence of any of the non ionic surfactants as there was no statistically significant difference between these values irrespective of the type and concentration used (P>0.05). All the granules were free flowing with angles of repose 0.05). All the formulations fitted into Korsmeyer and Peppas model and the release exponents (n) were between 0.49 and 0.86. This indicates that release of ibuprofen wax matrix followed anomalous transport, often termed first-order release. Non ionic surfactants influenced the release of drugs from the system studied hence, controlled amount of non ionic surfactant can be used to effectively enhance and modulate the release of drugs from such system.Keywords: Ibuprofen, non-ionic surfactants, dissolution profile, wax matrix, release mechanismJournal of Pharmaceutical and Allied Sciences, Vol. 7 No. 5 (2010

Investigation of Carnuba Wax as Matrix in the Formulation of Solid Lipid Microparticles for Controlled Release Application

This study was carried out to investigate the drug entrapment efficiency, release potential and drug release mechanisms of solid lipid microparticles (SLMs) prepared with different concentrations of two non ionic surfactants using carnauba wax as the lipid matrix. SLMs were prepared by melt dispersion technique, whereby the molten carnauba wax containing the drug (theophylline) was emulsified in heated aqueous phase with different concentrations of non ionic surfactants, followed by cooling at room temperature for recrystallization of the microparticles, which were  recovered. The prepared SLMs were characterized for their packing, flow properties, drug entrapment efficiency and encapsulated for dissolution testing. The dissolution data were analysed using zero order, first order and Higuchi drug release models. It was observed that all the SLMs prepared had a high drug entrapment efficiency >80%. Increase in surfactant concentration decreased the drug entrapment efficiency although the type of non ionic surfactant used had no significant effect on the drug entrapment efficiency (p>0.05). The drug release profile followed first order as well as Higuchi square root of time models. The results of this study show that it is possible to formulate SLMs with high drug entrapment efficiency when carnauba wax is used as lipid matrix. These prepared SLMs can be used effectively to modulate release of theophylline which will in turn improve patient compliance.Keywords: Solid lipid microparticles, drug entrapment efficiency, non ionic surfactants, drugrelease profile