Formulation development and statistical optimization of chronotherapeutic tablets of indometacin

Chronotherapeutic drug delivery offers a new approach in the pharmacologic interventions design for the effective treatment in the diseases which follows circadian rhythm. In the present study chronotherapeutic tablets of indometacin was designed to match the timing of rheumatoid arthritis treatment with the intrinsic illness timing. The developed chronotherapeutic delivery system consists of a core tablet containing the active ingredient along with osmogents and other excipients, which was coated with a swellable polymer, hydroxyl propyl methyl cellulose by compression coating technique. The time controlled release was achieved by coating the entire system with a combination of pH-independent polymer, Eudragit RS 100 and Eudragit RL 100 (1:1). The optimization technique using Box–Behnken design was employed for the selection of the ideal formula. The optimization procedure was validated, and the observed value of the ideal batch was found to be similar with the predicted values within 5% of predicted error. The formulation when administered at bed time starts releasing the drug after a lag time of 4?h and provides sufficient plasma concentration after 6?h of normal sleep. Thus, the tablets can be successfully used for the chronotherapeutic drug delivery of indometacin in the treatment of rheumatoid arthritis.     

Formulation optimization technique based on artificial neural network in salbutamol sulfate osmotic pump tablets

The aim of this study was to develop a formulation optimization technique in which an artificial neural network (ANN) was incorporated; 30 kinds of salbutamol sulfate osmotic pump tablets were prepared, and their dissolution tests were performed. The amounts of hydroxypropyl methylcellulose (HPMC), polyethylene glycol 1500 (PEG1500) in the coating solution, and the coat weight were selected as the causal factors. Both the average drug release rate v for the first 8 hr and the correlation coefficient r of the accumulative amount of drug released andtime were obtained as release parameters to characterize the release profiles. A set of release parameters and causal factors was used as training data for the ANN, and another set of data was used as test data. Both sets of data were fed into a computer to train the ANN. The training process of theANN was completed until a satisfactory value of error function E for the test data was obtained. The optimal formulation produced by the technique gave the satisfactory release profile since the observed results coincided well with the predicted results. These findings demonstrate that an ANN is quite useful in the optimization of pharmaceutical formulations.     

Electroflocculation for the treatment of wastewater from dairy food industry: scale-up of a laboratory reactor to full-scale plant

Clean Technologies and Environmental Policy - The aim of this work was to evaluate the scale-up of a laboratory reactor to full-scale plant for the electroflocculation of dairy food industry...     

Formulation, in-vitro release and therapeutic effect of hydrogels based controlled release tablets of propranolol hydrochloride

Matrix based controlled release tablets of Propranolol Hydrochloride (PHCL) were formulated using hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (sod. CMC) and their combinations. The in-vitro dissolution kinetics revealed a zero order release for selected drug, HPMC and sod. CMC combination. The selected formulation was evaluated in mongrel dog by recording the isoprenaline induced tachycardia and measuring the inhibition of tachycardia. The results showed the sustaining therapeutic effect of the formulation.     

Formulation,in-vitro release and therapeutic effect of hydrogels based controlled release tablets of propranolol hydrochloride

Abstract

Matrix based controlled release tablets of Propranolol Hydrochloride (PHCL) were formulated using hydroxy propyl methyl cellulose (HPMC), sodium carboxy methyl cellulose (sod. CMC) and their combinations. The in-vitro dissolution kinetics revealed a zero order release for selected drug, HPMC and sod. CMC combination. The selected formulation was evaluated in mongrel dog by recording the isoprenaline induced tachycardia and measuring the inhibition of tachycardia. The results showed the sustaining therapeutic effect of the formulation.     

Formulation and evaluation of Methocel K15M bioadhesive matrix tablets

Methocel K15M is a bioadhesive polymer. Its adhesion and bioadhesion characteristics were evaluated by shear stress measurement and detachment force measurement methods, respectively. The effect of pH on adhesion was studied, and it was found that the maximum adhesion was between pH 5 and pH 6. Adhesion strength at different parts of the sheep intestine was studied; in the duodenal portion of the intestine, the adhesion was maximum. Chlorpheniramine maleate and diclofenac sodium drugs are formulated with Methocel K15M as matrix tablets. In vitro release studies revealed that some of the formulations showed initial first-order behavior followed by zero-order release behavior.     

Formulation and evaluation of rapidly disintegrating fenoverine tablets: effect of superdisintegrants

The objective of this study was to formulate directly compressible rapidly disintegrating tablets of fenoverine with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration. Effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time was studied. Tablets were evaluated for weight variation, thickness, hardness, friability, taste, drug content, in vitro and in vivo disintegration time, and in vitro drug release. Other parameters such as wetting time, water absorption ratio ('R'), and drug-excipient compatibility were also evaluated. The disintegration time of the best rapidly disintegrating tablet formulation among those tested was observed to be 15.9 sec in vitro and 37.16 sec in vivo. Good correlation was observed between disintegration time and 'R' for each of the three superdisintegrants at the concentrations studied. Considering the 'R' values and disintegration time, crospovidone was significantly superior (p < 0.05) compared to the other superdisintegrants tested. Release of drug was faster from formulations containing 6% crospovidone (CP 6) compared to the marketed fenoverine (Spasmopriv(R)) capsules. Similarity factor 'f(2)' (51.5) between dissolution profiles of the rapidly disintegrating tablet formulation CP 6 and the marketed formulation indicated that the two dissolution profiles were similar. Differential scanning calorimetric studies did not indicate any excipient incompatibility, either during mixing or after compression. In conclusion, directly compressible rapidly disintegrating tablets of fenoverine with lower friability, acceptable taste, and shorter disintegration times were obtained using crospovidone and other excipients at optimum concentrations.     

Formulation of tablets containing an 'in-process' amorphized active pharmaceutical ingredient

The aim of this work was a preliminary study of the "in-process" amorphization of clopidogrel hydrogensulfate (CLP) as model drug during the production of tablets as dosage form. A solvent method was used for amorphization and the crystalline phase of CLP was detected by differential scanning calorimetry; the physical parameters of fresh and stored tablets were investigated. For the amorphous form, Aerosil 200 was selected as crystallization inhibitor as the most suitable of eight auxiliary agents. The optimum composition of the product for amorphization in the scaling-up process (100-fold) was 7 parts of CLP to 3 parts of Aerosil 200. In this scaled-up product, the amorphous CLP was fixed on the surface of microcrystalline cellulose. The tablet form further stabilized the amorphous form. Finally, the steps of an "in-process" amorphization are given as a protocol, which can promote stabilization of an amorphized active pharmaceutical ingredient.     

Systematic investigation of acicular ferrite formation on laboratory scale

By increasing the amount of acicular ferrite (AF) in the microstructure, steel toughness can be improved significantly. The steel composition, cooling rate, non-metallic inclusions and austenite grain size have a strong influence on the formation of AF. The present paper describes and compares two approaches to study AF formation in a titanium-deoxidised high-strength low-alloyed steel and its influencing factors on laboratory scale: route A simulates the formation of AF after heat treatment; route B simulates the formation directly after solidification of the melt. The formation of AF is essentially influenced by the former processing, which also changes the optimum cooling parameters substantially. (Ti,Mn)_xO_y and (Ti,Al,Mn)_xO_yS_z are the predominant active inclusion types in the investigated steel.     

Formulation development of allopurinol suppositories and injectables

Allopurinol was formulated into injectable and suppository dosage forms. The injectable formulation was prepared by dissolving allopurinol in a cosolvent system consisting of dimethyl sulfoxide (DMSO) and propylene glycol (v/v = 50/50). The stability of allopurinol in the cosolvent system was studied under accelerated storage conditions, and results indicate first-order degradation kinetics with an activation energy of 24.3 kcal/mol. The development of suppository dosage forms was performed by formulating allopurinol with polyethylene glycol (PEG) mixtures of different molecular weights. In vitro release profiles of suppositories formulated with different polyethylene bases were obtained in the pH 7.4 buffer solution using the USP 23 paddle method at 100 rpm. Results indicate that the release rate of the suppository formulations containing PEG 1500/PEG 4000 at the ratio (w/w) of 2.5/10 to 10/2.5 appeared to be similar. However, the addition of sodium lauryl sulfate in the suppository decreased the release rate of allopurinol significantly. A future study to establish in vitro/in vivo correlation (iv/ivc) is suggested.     

Ti-Zr-V non-evaporable getter films: From development to large scale production for the Large Hadron Collider

Non-evaporable getter (NEG) alloys after dissolution of their native oxide layer into the bulk are able to pump most of the gases present in ultra-high vacuum systems. The dissolution process, commonly called activation, is obtained by heating in vacuum. NEG materials can be sputter-deposited as a thin film on the inner wall of a vacuum chamber, transforming it from a source of gas into an effective pump. The most significant advance in the development of NEG films was the discovery of a very low activation temperature (180 °C for 24 h heating) in a large range of compositions of the Ti-Zr-V system. This favourable property was correlated with nanometric grain size of the film (about 3 to 5 nm).In addition to pumping, NEG films lead to reduced induced gas desorption and secondary electron yields. As a consequence, Ti-Zr-V films provide the optimum solution to most of the problems encountered in vacuum systems of modern particle accelerators for high energy physics and for synchrotron radiation facilities. In the near future the most significant benchmark for Ti-Zr-V films will be the Large Hadron Collider (LHC) presently under construction at CERN, where about 6 km of beam pipe are being coated. A dedicated magnetron sputtering facility has been built to cope with the high number of vacuum chambers (about 1200) and the tight production schedule.     

Formulation and evaluation of matrix type mucoadhesive tablets aimed at treating oral aphtha

Context: Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to the side effects of thrombocytopenia.

Objective: To avoid systemic side effects, a matrix type mucoadhesive tablet as a topical application preparation to treat oral aphtha was developed.

Methods: A mixture of hard fat with a low irritant property and mucoadhesive polymers was used as the matrix base, and indomethacin was used as a model drug.

Results: Among the water-soluble polymers, carbopol and xanthan gum increased the adhesive force of tablets prepared by the suspending method, but the tensile strength was not increased. Tablets containing ethylcellulose 10 or 45 (EC10, EC45) from a water-insoluble polymer increased the adhesive force and tensile strength. Tablets prepared by the dissolve-drying method containing EC45 showed a 1.8-fold increase of adhesiveness to the eggshell membrane compared with hard fat tablets, and showed a sustained release of the drug (17%) over an 8?h period. The drug release was increased to 28% by a modification to the dissolve-drying method using EC10.

Conclusions: Since this matrix type tablet has long-acting properties, adhesiveness and low irritating properties, its potential as a newly designed preparation to treat oral aphtha is suggested.     

Formulation of olanzapine nanosuspension based orally disintegrating tablets (ODT); comparative evaluation of lyophilization and electrospraying process as solidification techniques

Olanzapine (OLAN) as an antipsychotic agent has shown its potential in effective management of psychotic disorders however its use is limited because of its poor water solubility. The aim of present work was to improve solubility of OLAN by developing a stable nanocrystal based orally disintegrating tablets (ODTs), using hyperomellose as potential stabilizer. Comparative evaluation of electrospraying and lyophilization as solidification techniques was carried out to assess its effect on solid state properties of OLAN nanocrystals before transformation to ODTs.OLAN Nanosuspension was developed using antisolvent precipitation method and exhibited particle size, polydispersity index and zetapotential value of 223.1?±?1.5?nm, 0.105?±?0.4 and ?17.9?±?3.5?mV respectively. Solid powders obtained from both the solidification techniques were compared in terms of size after re-dispersion, particle morphology, surface area, pore volume and solid state of drug present. Subsequently ODTs were prepared from these powders with needful excipients and % amount dissolved was evaluated. Rate of dispersion was found to be higher for ODTs prepared using lyophilized powder (～84% in 5?min) while other characterization parameters were comparatively similar. Overall, Lyophilization resulted in powders with better bulk level properties in comparison to electrospraying process.     

Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases

Eugenol is the principle chemical constituent of clove oil and has been used to cure dental problems for ages. Eugenol is an integral part of the dentist's kit due to its analgesic, local anesthetic, anti-;inflammatory, and antibacterial effects. It is used in the form of a paste or mixture as dental cement, filler, and restorative material. This study reports the development and evaluation of controlled-release mucoadhesive tablets for gingival application, containing eugenol, which are prepared by taking carbopol 934 P and Hydroxypropyl methylcellulose (HPMC) K4M in the ratio of 1:2, 1:1, and 2:1. Incorporation of eugenol (10 mg) in a mucoadhesive formulation provides controlled release for a period of 8 hours, which is advantageous over conventional use. In vitro mucoadhesion measured as detachment force in grams and the formulations show good correlation in vivo. The release study indicates that increase in carbopol increases the release rate of eugenol from the formulation whereas HPMC retards it. Increased in vitro bioadhesion is related to HPMC content of the formulation. The release kinetics of eugenol in vitro correlates with the in vivo results. This indicates the increased potential of eugenol as antibacterial, local analgesic, and anaesthetic treatment.     

Formulation of tablets containing an ‘in-process’ amorphized active pharmaceutical ingredient

The aim of this work was a preliminary study of the “in-process” amorphization of clopidogrel hydrogensulfate (CLP) as model drug during the production of tablets as dosage form. A solvent method was used for amorphization and the crystalline phase of CLP was detected by differential scanning calorimetry; the physical parameters of fresh and stored tablets were investigated. For the amorphous form, Aerosil 200 was selected as crystallization inhibitor as the most suitable of eight auxiliary agents. The optimum composition of the product for amorphization in the scaling-up process (100-fold) was 7 parts of CLP to 3 parts of Aerosil 200. In this scaled-up product, the amorphous CLP was fixed on the surface of microcrystalline cellulose. The tablet form further stabilized the amorphous form. Finally, the steps of an “in-process” amorphization are given as a protocol, which can promote stabilization of an amorphized active pharmaceutical ingredient.     

Development of technologies for large scale production of titanium and magnesium metals at the defence metallurgical research laboratory,Hyderabad

Titanium has been finding increasing usage as a structural metal in aerospace and many non-aerospace sectors mainly due to its light weight, high strength and outstanding corrosion resistance properties. India is very fortunate to possess the world’s largest and richest mineral deposit for this metal. Early studies on the metal extraction during mid ’60s at the Bhabha Atomic Research Centre, Bombay and pilot plant studies at the Nuclear Fuel Complex, Hyderabad resulted in the establishment of a ‘Technology Development Centre’ at Defence Metallurgical Research Laboratory (DMRL), Hyderabad. DMRL has already demonstrated titanium sponge production feasibility in 2,000 kg batches by the conventional Krcll process and is presently engaged in the development of the more energy saving ‘combined process technology’ in 4,000 kg batches. Fused salt electrolysis is widely employed to produce magnesium metal in integrated titanium plants so as to regenerate magnesium from the by-product magnesium chloride. DMRL has developed magnesium electrolysis technology in a 30 kA monopolar, modular type cell and is now developing the multipolar cell technology in 7kA, 22·2 V, two-module cell equipped with five bipoles in each module. This paper traces the developmental efforts on titanium metal extraction in India and describes the current efforts underway at DMRL for developing the latest energy efficient and cost effective technologies for the large scale production of both titanium and magnesium metals.     

Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30?KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force – time curves revealed a direct relation of maximum disintegration force (F_max) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F_max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.     

Formulation and evaluation of diclofenac potassium fast-disintegrating tablets and their clinical application in migraine patients

The aim of this study was to prepare fast-disintegrating tablets (FDTs) of diclofenac potassium with sufficient integrity as well as a pleasant taste, using two different fillers and binders: Tablettose 70® and Di-Pac^®. Tablets were made with direct compression method. Tablet properties such as porosity, hardness, and disintegration time were determined. Diclofenac potassium determinations were carried out using a validated spectrophotometric method for the analysis of drug. Furthermore, in vivo experiments were carried out to compare the analgesic effect and the time to relieve migraine headache between the commercial tablets and FDTs of diclofenac potassium against placebo. Results showed that FDTs of diclofenac potassium with durable structure and desirable taste can be prepared using both fillers and binders but tablets prepared with Di-Pac had a better taste so the tablet formulation containing Di-Pac was chosen for in vivo experiments. Placebo controlled in vivo trial demonstrated that 50 mg diclofenac potassium, administered as a single dose of FDTs or commercial tablets, was effective in relieving the pain and both of them were superior to placebo.     

Correction to: Sustainable bioethanol and value‑added chemicals production from paddy residues at pilot scale

Clean Technologies and Environmental Policy - Biorefineries from paddy residues (rice straw and rice husk) have a high potential to satisfy human society’s need for sustainable fuel and...