The influence of fillers on theophylline release from clay matrices

Abstract: The objectives of this study were to investigate the suitability of magnesium aluminium silicate (MAS) (Veegum®) to control drug release of a model drug, theophylline, from tablet matrices. To this end, the performance of three commonly used fillers namely: lactose, microcrystalline cellulose (Avicel PH102; MCC), and pre-gelatinized starch, Starch 1500 PGS), were evaluated against Veegum®. The physico-mechanical properties of the tablet matrices were studied along with dissolution studies to determine the effect of single or binary mixtures of the excipients on the drug release pattern. A DSC hydration methodology was also employed to characterize the states of water present in the tablet matrices and to determine any impact on drug release. Formulations containing MAS alone produced compacts with the lowest hardness (4.5 kp) whereas formulations containing MCC alone produced the hardest tablets (17.2 kp). Dissolution studies suggested that matrices containing MAS alone released the theophylline quickest as compared to lactose, MCC or PGS. It was difficult to establish a trend of the bound and free water states in the tablet matrices; however the formulation containing only MAS had the highest bound water at 29 %. The results therefore show that theophylline does not interact with MAS. As such the dominant factor in controlling drug release using MAS requires interaction or intercalation with a cationic drug. In the absence of this however, other excipients can play a role in controlling drug release. Keywords: Veegum, clay matrices, DSC hydration, Magnesium aluminium silicate, filler

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

The influence of hydroalcoholic media on the performance of Grewia polysaccharide in sustained release tablets

Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375 N) than that of the native polysaccharide (82 N) and HPMC K4 M (146 N). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f2 = 60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f2 = 43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world

FORMULATION DEVELOPMENT, OPTIMIZATION & IN VITRO CHARATERIZATION OF LIQUISOLID COMPACTS OF AN OXICAM DERIVATIVE

The rationale of the current research was to investigate the in vitro dissolution properties of poorly water soluble piroxicam by utilizing liquisolid technology. Dissimilar liquisoli compacts were formulated using a factorial design to estimate the required quantities of powder and liquid ingredients to fabricate adequately flowable and compressible admixture. About 16 different formulations were developed using factorial design with carriers Neusilin (Magnesium aluminometasilicate)  and Avicel PH 102, binder PVP K-30 and vehicle PEG-400 as independent variables and Aerosil 200 is used as coating material. The In-vitro drug release from the LSC has used a dependent variable. The empirical method by Spireas and Bolton was applied to calculate the amounts of carrier and coating materials and obtained the improved flow characteristics and hardness by changing the proportion of carrier and coating materials. Liquid solid compacts were fabricated and evaluated for their tabletting properties. Fourier transform infrared (FTIR) analysis, differential scanning calorimetry (DSC) and X- ray powder diffraction (XRPD) were performed. The FTIR spectra showed disappearance of the characteristic absorption band of piroxicam (3338.78 cm-1) in liquisolid formulations which might be attributed to the formation of hydrogen bonding between the drug and liquid vehicle; this resulted in drug dissolution enhancement. A 23 factorial design is used and developed liquid soild compacts using Neusilin LSCN1 to LSCN8 and Avicel PH 102 LSCA1 to LSCA8. The physicochemical characterization of all formulations exhibited well within the specification limits with respect to weight variation, hardness, friability and content uniformity.  The In-vitro drug release from these liquid soild compacts was evaluated in 0.1 N HCl and the optimized formulation LSCA8 was compared with pure drug (capsule) and physical mixture (tablet). The release studies suggested that the liquisolid tablets outcome in higher release profile than pure active pharmaceutical ingredient and physical mixture due to enhance in surface and wetting properties of the active pharmaceutical ingredient. Liquid solid compacts technique confirmed the enhanced dissolution rate of oxicam derivative, which in turn promotes in enhancing bioavailability. Keywords: Piroxicam, Factorial design, Solubility, Dissolution rate, Avicel PH 10

Formulation of Metformin HCl Floating Tablet using HPC, HPMC K100M, and the Combinations

Floating tablet is one of the most suitable dosage forms that used for delivering long term drug release. The objective of this study was to evaluate Hydroxypropyl cellulose (HPC), Hydroxypropyl Methyl Cellulose (HPMC) K100M, and the combination as matrix in manufacturing floating tablets. Metformin HCl, an anti-diabetic, was used as a drug model. Metformin HCl floating tablet was manufactured by wet granulation method in three formulas using variation of matrix, which were 40% of HPC (F1), 40% of HPMC K100M (F2), combination of 20% HPC and 20% HPMC K100M (F3). Prior to tablet compaction, evaluation for granules were done which included moisture content, angle of repose using, bulk and tapped density, Hausner ratio, and compressibility. The evaluations of floating tablet were physical properties, floating ability, and in vitro drug release. The average of floating lag time for F1, F2, F3, were 7 minutes 13 seconds; 5 minutes 27 seconds; and 14 minutes 5 seconds, respectively. In addition, the floating time for F1 was 3 hours 16 minutes whereas F2, F3 were more than 48 hours. F2 showed the best floating ability to retain the drug release, which was 84.68% over 8 hours, while F1 and F3 were completely dissolved less than 6 hours.

MODEL AND RELEASE PATTERN OF WATER SOLUBLE DRUG FROM NATURAL-POLYMER BASED SUSTAINED RELEASE TABLET DOSAGE FORM

Objective: The aim of this research was to investigate and evaluate the drug release characteristics (models and drug release profiles) using natural polymers (pectin, carrageenan and glucomannan) in water soluble drug of sustained release tablet. Methods: Captopril was used as drug model. Tablet were prepared using wet granulation method. Pectin, carrageenan and glucomannan were used as matrix with concentration 20%, 30% and 40%" with "matrices with various concentration. Physyical properties inpections were conducted on granules and tablets. Dissolution test using apparatus II USP model with 50 rpm of speed rotation, 900 ml of HCl 0.1N as medium. The results were analyzed statistically by MANOVA, dependent model and independent model. Results: The results showed that enhancement of matrix concentrations decreased the fluidity and compact-ability. Drug release of soluble drug using pectin as matrix not significant different than without matrix. Conclusion: Tablet using glucomannan and carrageenan as matrix controlled the drug release with initial burst release effect. Weibull models was the best fitting model of release kinetics with the highest coefficient of determination and similarity between predicted and observed data  and the release mechanisms were controlled by anomalous transport

Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz

AbstractEfavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins)

FORMULATION DEVELOPMENT AND CHARACTERIZATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS OF LORATADINE

Objective: The main objective of the research work is to develop a single unit non-effervescent drug delivery system of Loratadine (LTD) by direct compression process to prolong the gastric residence time (GRT). Methods: LTD non-effervescent tablets were prepared with different polymers like hydroxypropyl methylcellulose (HPMC) K15M, HPMC K100M (i.e.: 1:1, 1:2, 1:3) as release retardants. Glyceryl behenate (Compritol 888 ATO) and Glyceryl palmitostearate (Precirol ATO 5) were used (1:1, 1:2, 1:3) as low-density lipids to impart buoyancy for longer period. Results: The drug (LTD) and excipient (i.e. HPMC, low-density lipid aids, etc.,) interaction studies were carried out by Fourier Transform Infrared Spectroscopy (FTIR) and there was no likely interaction involving them. The developed LTD floating matrix tablets were characterized by pre and post-compression parameters and all results were, found within the pharmacopoeial limits. The cumulative percentage of drug release ranges from 56.87±0.25 % (F12) to 99.87±0.09 % (F2). The drug release profiles of the all formulations (F1 to F12) were subjected to various pharmacokinetic parameters and the optimized formulation (F3) followed the Korsmeyer Peppas (R2=0.996) model with non-Fickian diffusion (n>0.5). The obtained data by radiographic images of F3 formulation showed the GRT is 6±0.5 h (n=3). Conclusion: Hence, from all evaluation studies, it was evident that F3 formulation was optimized (99.82±1.63 % drug release in 12 h)