Three-layer Tablets Research Articles

Design and Optimization of Ibuprofen and Ranitidine Hydrochloride TriLayer Tablets in Immediate Release Formulation by Quality by Design.

The current trend in pharmaceutical process development and optimization is known as quality by design (QbD). This methodical approach is founded on the concept that quality should be integrated into the product from the start, rather than assessed after manufacture. In this study, we demonstrate methods to improve the process parameters for making tri-layer tablets by applying QbD principles in a methodical way. Dependent elements with high to medium impact on the process. According to the study’s results, all systems showed signs of instant release. It appears that the structure of each formulation and the properties of the polymer utilized have a significant impact on the rate and mechanism of drug release. Substantial medication release is observed in the three-layer formulations. Both the pace and mechanism of drug release are significantly affected by the tablet’s geometrical features and structure, as well as the weight and thickness of the barrier layers. While data suggested that Fickian diffusion was primarily responsible for drug release in two-layer tablets, three-layer tablets showed signs of either anomalous diffusion or erosion/relaxation. Therefore, the drug was stabilized as immediate-release directly compressible triple layered Average core weight of tri-layered tablets (mg) was 1000 for ibuprofen, 100 for placebo and 200 for ranitidine, thickness (mm) was 9.00 ± 0.3, hardness (N) was 110 ± 25, core tablet weight was 1300.000 ± 2% mg and coated tablet weight was 1325 mg. Using other moisture-sensitive medications. This study provides the foundation for future research into optimizing the properties of tablets made by direct compression.

Development of a Novel Controlled-Release Tablet of Pregabalin: Formulation Variation and Pharmacokinetics in Dogs and Humans.

BackgroundNovel three-layered (TL) tablet systems were compared with both monolithic matrix (MM) formulations and a commercial immediate-release (IR) capsule to develop once-a-day (OAD) pregabalin tablets.MethodsThe physical properties of the TL tablets, including dissolution and swelling rates, were compared with those of the MM tablets and the pharmacokinetic parameters of the TL tablet were compared with those of an IR capsule in beagles and humans.ResultsOur results indicated that the same amount of a hydrophilic polymer in the formulations had similar dissolution profiles at 12 h, regardless of the tablet geometry. However, the degree of tablet swelling differed, with larger amounts of polymer in the tablets showing a greater degree of swelling. In addition, TL tablets swelled more rapidly compared with MM tablets. For the pharmacokinetic study of the TL tablet, the beagles demonstrated absorption results similar to those of an IR capsule, whereas the humans demonstrated low total absorption compared with an IR capsule. The time of the peak plasma concentration at 6 h in the fed state of humans coincided with the results of the study on beagles.ConclusionThe novel TL tablet system of pregabalin may prove to be helpful in developing improved formulations with better continuous drug absorption for OAD administration.

Modified In Vitro Release of Melatonin Loaded in Nanofibrous Electrospun Mats Incorporated Into Monolayered and Three-Layered Tablets

Modified release tablet formulations with melatonin (MLT) are clinically more useful in initiating and maintaining sleep in elderly insomniacs, compared with those designed for immediate release. Aiming at the modified release of MLT, monolayered and 3-layered tablets, incorporating nanofibrous mats composed of cellulose acetate and polyvinylpyrrolidone loaded with MLT, were prepared and studied. In vitro dissolution profiles of MLT in gastrointestinal-like fluids revealed tableting pressure/pH-dependence. The release of the hormone from physical mixture tablets was generally slower from the nanofibers-based tablets, thus exhibiting in the latter case properties that are necessary for the control of both the sleep-onset and the maintenance dysfunctions. The nature of the excipients (hydroxypropylmethylcellulose or lactose monohydrate) used in this study to produce 3-layered tablets was also found to affect the release of MLT, adjusting it to the endogenous hormone's chronobiotic profile. The release of MLT from formulation F(nf)2 (nanofiber mats incorporated into 3-layered tablets containing lactose monohydrate both in the upper and lower layers) was found to be in closer alignment with these effects than the other delivery systems.

FORMULATION AND EVALUATION OF ZOLPIDEM TARTRATE LAYERED TABLETS BY MELT GRANULATION TECHNIQUE FOR TREATMENT OF INSOMNIA

Objective: The main objective of this study was to formulate and evaluate the sustained release matrix tablets of zolpidem tartrate, using hydrogenated vegetable oil as a polymer.Methods: Various formulations were prepared by melt granulation method using concentrations Lubritab, HPMC K100, and lactose monohydrate. The optimized formulations were prepared as three-layered tablets using HPMC K4M.Results: All formulations blend were evaluated for various precompression parameters were found to be good. The drug and excipients compatibility study was performed, and the study revealed that there was no interaction between drug and excipients. The compressed tablets were evaluated for various physicochemical parameters. The initial release from the matrix tablet was higher which was reduced by the preparation of three-layered tablet using HPMC K4M. The initial release was controlled to 10–12%, but the complete release was not there in 12 h. To get the complete release of the drug pore forming agent such as lactose and HPMC K100 was included in the matrix. ZT22 and ZT25 were considered as optimized formulations, and the drug release at 12th h is 98.85% and 98.3% respectively. The optimized formulation was subjected to stability studies for 3 months as per ICH guidelines for climate zone III and was found to be stable.Conclusion: Difficulties with sleep onset and or sleep maintenance can be treated successfully using the optimized formulations ZT22 and ZT25 for the prompt onset of action of the drug over a prolonged period of time which may lead to improved efficacy, better patient compliance.

Modified geometry three-layered tablet as a platform for class II drugs zero-order release system

Purpose: To optimize a geometrical design of three-layered tablets for controlling the release of indomethacin (Ind) as a BCS class II model. Methods: The core formulation was optimized to ensure non-disintegrating tablet with a slow release behavior. Three-layered tablets were prepared by a single-step direct compression method by manual feeding of a hydrophobic layer in the bottom followed by Ind core layer and another hydrophobic layer at the top using 6 and 12 mm round compression sets. Four batches were prepared, differing only in either thickness of the drug layer or tablet diameter. A number of factors were studied, including tablet thickness to diameter ratio and drug layer surface area. The rate of Ind released was determined using USP dissolution apparatus I. Results: The optimum drug layer formulation contained Ind (40%), polyvinylpyrolidone K30 (40 %), and ethyl cellulose (20 %). The t50% (time taken for 50 % drug release) for the four three-layered tablet batches with varying diameter to thickness ratios were in the range of 1.5 to 3.7 h. The diameter to thickness ratios were in good correlation with % Ind release after 4 h (R2 = 0.94). It was found that all batches complied with zero order kinetic model. Conclusion: The new one-compression phase applied in this study is successful in producing threelayered tablets in a single-step with very good mechanical attributes. The approach of designing a controlled release tablet via control of the surface area of drug release is feasible for non-swelling matrices. Keywords: Controlled release, Indomethacin, BCS class II drugs, Ethyl cellulose, Release kinetics, Direct compression

Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect

In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen.An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers.The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating.

Sustained Release Formulation and Characterization of Nifedipine Three-layered Tablet Using Various Polymers

니페디핀은 고혈압 치료제로 쓰이는 약물로 난용성이기 때문에 용출률의 개선이 필요한 약물이다. 또한 반감기가 1.5~2시간 정도로 짧기 때문에 약물방출을 서방화시킬 필요성이 있다. 본 연구에서는 니페디핀의 약물 방출을 조절하기 위하여 다중층 정제를 통한 24시간 방출제어를 목표로 하였다. 다중층 정제는 윗층과 아래층 그리고 가운데층의 세층으로 이루어지며 윗층과 아래층은 gel-forming 고분자를 이용하여 방출조절을 시도하였다. 가운데 층은 니페디핀의 용출률 향상을 위해 니페디핀과 폴리비닐프롤리돈 K30의 고체분산체를 제조하여 사용하였다. 고체분산체 분석을 위한 SEM, XRD 그리고 DSC분석을 실시하였으며, 인공장액(pH 6.8)에서 생체 외 용출거동을 24시간동안 실시하였다. 실험 결과, 여러 종류의 친수성 고분자 종류 중 하이드록시프로필 메틸셀룰로스 K15M을 사용한 니페디핀 삼중층 제형이 가장 좋은 서방형 패턴과 용출률을 확인할 수 있었다. 이를 통해 니페디핀의 서방화 가능성을 확인할 수 있었다.

Comprehensive evaluation of layer separation tendency of novel three-layered tablets with geometric and mechanical properties

The layer separation tendency of a novel three-layered matrix tablet was investigated according to various physical properties and novel experiments. Even though layer separation did not occur during manufacturing process and storage, it was observed during a dissolution test depending on the mid-layer formulation. According to the powder properties of the mid-layer substances, Form A, which had higher porosity and lower density than Form B, displayed a tendency of layer separation. These properties correlated with the degree of absorption of the aqueous medium into the mid-layer, which was evaluated by water uptake and mass loss tests. Water uptake and mass loss profiles of the formulations were similar, but the mass loss property of Form A was about 5% higher at the time points, due to the faster dissolution rate of the mid-layer in the first 0.5h. Using a texture analyzer, the layer separation force of the system and adhesion force between the barrier layers were evaluated to understand the correlation between the geometric property and layer separation tendency. During the first 0.5h, the wrapping property of the swollen barrier layers significantly affected the layer separation tendency. The drug release profiles of two formulations could be divided into three stages on the basis of their geometric property as it showed a sigmoid-type. However, for the first stage (about initial 1h in duration), the drug release of Form A was more than Form B due to the mid-layer's powder properties. The results provided valuable information for detailed understanding of issues in the development of a multi-layered system and indicated the importance of a well-designed tablet formulation and manufacturing process.

Evaluation of drug delivery profiles in geometric three-layered tablets with various mechanical properties, in vitro–in vivo drug release, and Raman imaging

Even though various multi-layered tablets have been developed for sustained release formulations, evaluations of mechanical properties during dissolution with drug release and imaging in the tablets have been limited. A novel geometric system consisting of an inner immediate release layer and two extended release barrier layers with swellable hydrophilic polymers was suggested as a once-a-day formulation. To evaluate drug release mechanisms with geometric properties, various mechanical characteristics during swelling were investigated to comprehend the relationship among in vitro drug release, human pharmacokinetics, and geometric characteristics. Imaging of drug movement was also studied in real-time using Raman spectroscopy. Drug delivery in the tablets might be divided into three processes through the geometric properties. When exposed to aqueous environments, the drug in the mid-layer was released until wrapped by the swollen barrier layers. Then, the drug in the mid-layer was mainly delivered to the barrier layers and a small amount of the drug was delivered to the contact region of the swollen barrier layers. Finally, the delivered drug to the barrier layers was consistently released out in response to the characteristics of the polymer of the barrier layers. Using Raman spectroscopy, these processes were confirmed in real-time analysis. Moreover, in vitro drug release profiles and human pharmacokinetics showed consistent results suggesting that drug release might be dependent on the various geometric properties and be modified consistently during the formulation development.

Immediate release three-layered chewing gum tablets of fenoprofen calcium: preparation, optimization and bioavailability studies in healthy human volunteers

A three-layered gum tablet (1800 mg), containing 200 mg of Fenoprofen Calcium (Fn) with an inner core containing the drug, and two external layers containing antiadherent lubricant, has been prepared using direct compression. A 23 factorial plan has been designed to evaluate the effect of formulation variables namely, Pharmagum® M concentration, Maltodextrin type, and Co-adjuvant type on the release characteristics of Fn from the prepared tablets. The formula consisting of 65% Pharmagum® M, 75% Maltodextrin DE 39 and 5% Talc comparatively exhibited the highest release (66.59% ± 2.39) in the mouth after 5 min of chewing. Binary and ternary β-cyclodextrin (β-CD) complexation was adopted to enhance the release of Fn from the selected gum tablet. The highest significant release (p < 0.05) was achieved from the lyophilized ternary complex containing 100 mg of Fn in presence of polyvinylpyrrolidone (PVP K25), exhibiting a release of 88.25% ± 0.93 after 5 min of chewing. The relative bioavailability of the selected gum tablet was found to be 166.06% compared to Nalfon® 200 mg capsules. Reduction of the dose to 100 mg exhibited faster absorption rate than Nalfon® capsules. The obtained results suggest the possibility of reducing the dose of Fn in chewing gum.

A novel three-layered tablet for extended release with various layer formulations and in vitro release profiles

A novel three-layered tablet consisting of a water-soluble mid-layer and two barrier layers with swellable polymers was investigated to develop a preferable once-a-day formulation containing terazosin HCl as a hydrophilic model drug. When the tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. It facilitated the tablet to absorb a lot of water compared with monolithic matrix. Moreover, formation of a lot of pores in the tablet during dissolution could be observed, suggesting significant water absorption in the inner matrix and swollen polymers of the tablet. Barrier layers influenced drug release profiles significantly, potentially due to differences in viscosity after swelling that produce different diffusion coefficients and mechanical strength. The drug in the mid-layer showed the sigmoid type of release pattern because a period of time might be needed to release the drug from the mid-layer through the barrier layers, but the drug in barrier layers showed the typical release pattern of monolithic matrix. As the amount of water-soluble excipient in the mid-layer increased, the degree of swelling also increased, suggesting that its amount in the layer may affect the overall swelling properties of the tablet. It was also shown that more hydrophilic mid-layer caused faster erosion rate, which was related to the results of swelling property. The three-layered tablets showed more consistent release kinetics than the matrix tablets. These results can give good information for the development of sustained drug delivery systems, especially once-a-day administration.

Formulation Variation and in Vitro-in Vivo Correlation for a Rapidly Swellable Three-Layered Tablet of Tamsulosin HCl

In order to develop a preferable once-a-day oral tablet formulation, various formulations of three-layered tablets containing tamsulosin HCl as a hydrophilic model drug were evaluated and compared with a commercial reference, tamsulosin OCAS®. When the test tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. Volume expansion showed faster and enough swelling of the three-layered tablet up to 2 h. Larger amount of barrier layers caused reduced release kinetics and a high molecular weight polymer showed more resistance against agitation force. A formulation with water-soluble mid-layer showed fast erosion decreasing its volume significantly. On the pharmacokinetic study, the mean ratio of area under the curve (AUC) and C(max) for the test formulation to the reference was 0.69 and 0.84, respectively, showing that the absorption of the drug was less complete than the reference. Plasma concentration at 24 h of the test formulation was higher than the reference. The Wagner-Nelson method showed that decreased initial dissolution rate might be the cause of the less complete absorption. On considering in vitro-in vivo correlation (IVIVC), level A, the reference (R²=0.981) showed more linear relationship than the test (R²=0.918) due to the decreased dissolution and absorption rate of the formulation. This result suggests that the in vitro dissolution profiles and release kinetics might be useful in correlating absorption kinetics as well as overall plasma drug concentration-time profiles for formulation studies.

Utilization of Hydrophilic Swellable Polymers as Carriers for Sustained Drug Delivery from Matrices and Three Layer Tablet Systems

The purpose of this research was to develop and evaluate different sustained release preparations, using swellable polymers as carriers in the form of matrices and three-layer tablets. These preparations may offer a number of therapeutic advantages over immediate release dosage forms in drug delivery. The materials used for the fabrication of these systems were hydrophilic swellable polymers namely Metolose, Polyox, Xanthan gum and an erodible material Gantrez, acting as drug(diclofenac sodium) carriers. The powder characteristics determined for these polymers suggest good flowability with the exception of Gantrez. The addition of 1% of magnesium stearate resulted in improved flow properties for all polymers including Gantrez. Tablets were prepared by direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core containing the drug. Our findings show that both preparations exhibit sustained release characteristics; also the structure of the device considerably affects the drug release and the release rate. Furthermore erosion and swelling greatly influence the overall behavior, function and performance of the systems. Finally kinetic analysis studies indicated that the drug release mechanisms were also affected by these effects.

Formulation Study and Evaluation of Matrix and Three-Layer Matrix Tablets Oral Controlled Drug Delivery System Based on Xanthan Gum and Locust Bean Gum

The present study was carried out to develop oral controlled release matrix tablets and three layer matrix tablets of highly water soluble diltiazem HCl using natural polymers Xanthan gum (XG), locust bean gum (LBG) and a mixture XG: LBG in 1:1 ratio as matrix forming agent, and anionic Sodium Carboxyl Methyl Cellulose as release retardant layer on the matrix core, Di calcium Phosphate (DCP) and Micro crystalline Cellulose (MCC) as fillers. Matrix core tablets were prepared with by granulation technique.The characterization of physical mixture of drug and excipeints was performed by infra red spectroscopy. The finding of the study indicated that the matrix tablets prolonged the release, but predominantly in a first order fashion, layering with SCMC granules on the matrix core, provided linear drug release with zero order kinetics. The influence of layers on matrix core and release rate was described by the peppas equation, model independent approach, Mean dissolution time (MDT) and dissolution efficiency (D.E 8%). The addition of SCMC layers on the matrix core could notably influence the dissolution behavior and mechanism of drug release. Increasing the quantity of layers caused decreased values of k and increased n value, in a linear relationship. MDT for matrix tablet (S6) and three layer matrix tablets (S6L3) was found to be 5.16h and 11.97h, D.E 8% was 76.23% and 66.21% respectively. These indicated that the release of drug is slower from the three layer matrix tablets. Type of fillers has a limited effect on the drug release mechanism from matrix tablets. Stability studies revealed that the formulation was stable at 45°±2°C and 75±5%RH. Hence natural polymer as matrix core and anionic polymer SCMC as retardant layer in the form of three layer matrix tablets provided the zero order release of highly water soluble Diltiazem HCl.

Optimization and In vivo Pharmacokinetic Study of a Novel Controlled Release Venlafaxine Hydrochloride Three-Layer Tablet

Several matrix tablet formulations (hydrophilic-based, wax-based, and three-layer tablets) were designed for controlling the release of the highly water soluble drug, venlafaxine hydrochloride (VenHCl) for once-daily administration. The three-layer tablets consist of non-swellable, compritol-based middle layers containing the drug to which hydrophilic top and bottom barrier layers were applied. A 2(3) full-factorial design was employed for optimization and to explore the effect of different variables on the release rate of the drug from the three-layer tablets. The optimized levels of each independent variable were based on the criterion of desirability. The calculated values of f(1) and f(2) were 4.131 and 79.356, respectively; indicating that the release profile of the optimized PEO layered tablet formulation is comparable to that of the target release model. The pharmacokinetic parameters of VenHCl from the optimized three-layer tablet was compared to the marketed extended release capsule as a reference in healthy human subjects using a randomized crossover design. In this study, the 90% confidence interval for AUC(0-24) and AUC(0-∞) are within (0.8-1.25), which satisfied the bioequivalence criteria. It could be concluded that a promising once-daily extended-release three-layer tablet of the highly water soluble drug, VenHCl, was successfully designed.

A Design and Evaluation of Layered Matrix Tablet Formulations of Metoprolol Tartrate

The aim of this paper was to evaluate the performance of different swellable polymers in the form of layered matrix tablets to provide controlled therapeutic effect of metoprolol tartrate for twice daily administration. Seven different swellable polymers (carrageenan, hydroxypropylmethyl cellulose, pectin, guar gum, xanthan gum, chitosan, and ethyl cellulose) were evaluated alone or in combination as release-retardant layer. Tablets were tested for weight variation, hardness, diameter/thickness ratio, friability, and drug content uniformity and subjected to in vitro drug-release studies. In addition, the target-release profile of metoprolol tartrate was plotted using its clinical pharmacokinetic data, and the release profiles of the tablets were evaluated in relation to the plotted target release profile. Carrageenan was determined as the best polymer in two-layered matrix tablet formulations due to its better accordance to the target release profile and was selected for preparing three-layered matrix tablets. Carrageenan formulations exhibited super case II release mechanism. Accelerated stability testing was performed on two- and three-layered matrix tablet formulations of carrageenan. The tablets were stored at 25 degrees C/60% relative humidity and 40 degrees C/75% relative humidity for 6 months and examined for physical appearance, drug content, and release characteristics. At the end of the storage time, formulations showed no change either in physical appearance, drug content, or drug-release profile. These results demonstrated the suitability of three-layered tablet formulation of carrageenan to provide controlled release and improved linearity for metoprolol tartrate in comparison to two-layered tablet formulation.

Two- and three-layer tablet drug delivery systems for oral sustained release of soluble and poorly soluble drugs

Background: Multilayer tablets are gaining importance in oral sustained drug delivery. They consist of an active matrix core and one or more layers applied during tableting which may act as barriers and regulate drug release. Objective: To examine the release performance of two model drugs, diclofenac sodium and furosemide, from two- and three-layer drug delivery systems using as carriers hydrophilic swellable polymers, namely, Metolose, Polyox, Xantham gum, and an erodible material Gantrez. Results and discussion: All prepared formulations demonstrated sustained release profiles. They also indicated that the carrier characteristics (particularly swelling-expansion, erosion-dissolution) and drug solubility in combination with tablet structure considerably influenced the performance of examined formulations as well as their mode and mechanisms of release. In general our findings show that the differences in drug release between the two- and three-layer tablets are small as it appears that two-layer tablets exhibit a slightly higher release. Because of its greater erosion Gantrez formulations displayed faster release relative to Xantham gum, as did Metolose formulations compared to Polyox formulations. A faster release rate was also noted with diclofenac formulations compared to those of furosemide because of diclofenac's higher solubility mainly seen at early time period. Conclusions: All three-layer Gantrez tablets containing either diclofenac or furosemide and the two-layer furosemide formulation demonstrated a biphasic release. The above indicate that both structures may be used successfully for sustained release drug delivery. In addition the use of multilayer tablets, consisting of materials with suitable properties, may result in modulation of drug release.

Pharmacokinetics and pharmacodynamics of a new ACT formulation: Artesunate/Amodiaquine (TRIMALACT®) following oral administration in African malaria patients

A new fixed-dose combination of artesunate (AS) plus amodiaquine (AQ) (TRIMALACT) was recently developed for the treatment of uncomplicated falciparum malaria. The originality of this combination lies in its galenic formulation which consists of a three-layer tablet with two layers containing each of the active ingredients, i.e. AS and AQ, and these are separated by a middle layer containing an antioxidant compound. To evaluate the efficacy and tolerability of this combination, adults with uncomplicated malaria received three administrations of two tablets (100:300 mg AS/AQ) in a 24-h interval, in Democratic Republic of Congo. Parasitemia and fever were measured and the plasma levels of parent compounds and metabolites [dihydroartemisinin (DHA) and monodesethylamodiaquine (MdAQ)] were determined by high-performance liquid chromatography. In addition, we determined the prevalence of molecular markers of resistance to chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). The AS/AQ combination TRIMALACT demonstrated a good efficacy resulting in an excellent clinical and parasitological response rate of 100% after correction for PCR results. Treatment regimen was well tolerated. The main disposition parameters to AS+AQ were: for DHA, AUC = 632 +/- 475 ng h/ml and Cmax = 432 +/- 325 ng/ml, and for MdAQ = 14268 +/- 4114 ng h/ml and Cmax = 336 +/- 225 ng/ml (mean +/- standard deviation). Parasite genotyping show high frequencies of molecular SP- and CQ-resistance markers with more 80% of the samples showing more than three mutations linked to SP resistance and 93.48% carrying parasite with the CQ-resistant haplotype. This study shows that the AS/AQ combination TRIMALACT is safe and effective in the treatment of highly drug-resistant falciparum malaria.

Formulation Variables Influencing Drug Release from Layered Matrix System Comprising Chitosan and Xanthan Gum

The purpose of this study was to investigate the formulation variables influencing the drug release from the layered tablets containing chitosan and xanthan gum as matrix component. Increasing the amount of lactose could diminish pH sensitive release behavior of these matrix tablets. Effect of formulation variables on drug release from the prepared three-layered matrix tablets was investigated. The amount of drug loading did not affect the drug release which was influenced by the hydrodynamic force and the matrix composition. An increase in stirring rate correspondingly increased the release rate. Moreover, incorporation of soluble diluents in core or barrier could enhance the drug release. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was carried out to study the drug release mechanism. Most dissolution profiles of the prepared three-layered tablets provided a better fit to zero order kinetic than to first order kinetic and Higuchi's equation.

Variables Influencing Drug Release from Layered Matrix System Comprising Hydroxypropyl Methylcellulose

The purpose of this study was to prepare and evaluate layered matrix tablets of propranolol HCl containing HPMC and phytowax as matrix component using direct compression technique. Layering with this polymeric matrix could prolong the release of drug and shift the release pattern approach to zero order as described from the least square curve fitting. Increasing the amount of coating layer could apparently prolong the drug release. The longer lag time of drug release from one planar apparently when the amount of coating layer was increased. HPMC concentration and compression force did not affect the drug release from this three-layer tablet. The drug release from this three-layer tablet was influenced by hydrodynamic force. An increase in stirring rate was a corresponding increasing in the release rate. From photoimage and SEM, gel mass of HPMC was increased with time during dissolution and covered the core surface, therefore dissolved drug molecules were allowed to diffuse out from the core through the polymer network of gel layer containing the porous structure. This suggested that HPMC and phytowax could be fabricated into the layered matrix tablet exhibiting sustained drug release.