Degradation Kinetics of Thiamine Hydrochloride in Directly Compressed Tablets II: Reliability of Accelerated Stability Testing for Evaluating Tablet Formulations

Abstract

Directly compressed thiamine hydrochloride tablets formulated with single or binary blend of vehicles were used in this investigation. The change in the physical characteristics of vitamin tablets stored under different relative humidity conditions was statistically assessed and scored by relative ranking. Although Emcompress is known to accelerate drug decomposition (1,2) the results obtained with tablets formulated with this vehicle alone or in combination with other vehicles failed to show that the use of this vehicle may give rise to any discernible changes in the physical characteristics of the tablets. Although formulations containing Celutab as the vehicle are chemically stable (2) the tablets compressed with this vehicle showed a high degree of change in physical characteristics. The results obtained in this study indicate that Avicel alone or a blend of Avicel with either Celutab or Anhydrous lactose are suitable vehicles for the manufacture of thiamine hydrochloride tablets of high stability characteristics.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Abstract

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

Dissolution of Directly Compressed Thiamine Hydrochloride Tablets

Abstract

Directly compressed thiamine hydrochloride tablets with varying concentrations of different vehicles as well as their binary blends, were prepared for this investigation. The results showed that, formulated tablets with avicel anhydrous lactose and celutab completely dissolved within short times. First order mechanism was reported for the tablets prepared with single vehicles. The dissolution rate constant “K”, was a function of disintegration constant “D” of the tablets by the relation In K = a + n In D. In addition to that, it is proved that, “K” of produced tablets of short disintegration times was a function of the contributed vehicle concentration “C” by the relation, I/K = A exp. + NC.

On the other hand, (T 50%) of thiamine hydrochloride in a given batch was a function of its disintegration time.     

Compaction Behaviour of Musol,A New Direct Compression Vehicle

Abstract

The compaction characteristics of Musol, a new autocompressible vehicle derived through chemical modification of mucuna gum was investigated. Avicel PH 101, Zeparox and Encompress were used as reference tablet vehicles. Values of the mean yield stress derived from the analysis of Heckel plots indicate that Musol consolidates principally by plastic deformation, The effect of lubrication and recompression on friability, tensile strength and re-working potential of the tablets prepared with the vehicles were determined. While Avicel PH 101 yielded the strongest tablets, Musol showed the highest re-working potential for lubricated and un-lubricated slugs. On the basis of friability, tensile Values of strength and re-working potential, Musol than the grades of Zeparpx or Encompress performed better used in the study.     

Preparation and Evaluation of Directly Compressed Medazepam Hydrochloride Tablets

Medazepam, the well known benzodiazepine derivative used as a transquillizer and in alcohol withdrawal, was prepared in directly compressed tablets. The directly compressible vehicles which were used. singly or in binary blends 1:1, were Avicel, Lactose, STA-Rx 1500 Emcompress and the recently introduced vehicle compactrol. It was found that Avicel and Emcompress represent the most suitable single vehicles used for the preparation of Medazepam hydrochloride tablets. In case of binary blends it was found that the best quality batches were prepared using Avicel Emcompress blend 1:1. Physical characteristics including uniformity of weight, thickness, hardness, friability were investigated for the prepared batches. The effect of directly compressible vehicle variation on the uniformity of drug content and the dissolution rates of Medazepam hydrochloride tablets was also studied.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.     

Accelerated Tests in Relation to Shelf-Life of Multivitamin Liquid Preparations

Abstract

Chemical kinetics for the decomposition of vitamin A, vitamin B₁, sodium pantothenate, folic acid and vitamin B₁₂ were studied at higher temperatures in the case of two multi-vitamin preparations. Vitamin A, vitamin B₁ and sodium pantothenate were found to decompose in accordance with the first order reaction at higher temperatures, whereas folic acid and vitamin B₁₂ did not follow first order kinetics. It was concluded that, in the cases of multivitamin preparations, accelerated study at higher temperatures was feasible only in the case of vitamin A, vitamin B₁ and sodium pantothenate.     

Modified Drug Release From Beads Prepared with Combinations of Two Grades of Microcrystalline Cellulose

Abstract

In previous work, the use of binary drug diluent mixtures with various grades or types of microcrystalline cellulose were shown to exhibit varying degrees of release from beads prepared by extruder/marumerizer technology.

In this work beads of suitable physical appearance were prepared with varying proportions of two grades of microcrystalline cellulose (Avicel PH-101 and Avicel RC-581) and 10% drug. In-vitro dissolution results varied with the proportion and the grade of the microcrystalline cellulose and with the dissolution medium utilized. Microcrystalline cellulose beads remained intact in water or in acid, but beads with the microcrystalline cellulose/carboxymethylcellulose sodium product exhibited gel structures in water and remained as beads in acid. The quantity of gel formation increased with an increasing level of the carboxymethylcellulose sodium product.     

Effect of package light transmittance on the vitamin content of milk,part 3: Fortified UHT low‐fat milk

This work is the third and last part of a milk study evaluating the effect of package light transmittance on the vitamin content of milk, in this case on fortified UHT low‐fat milk. The milk was stored under light with an intensity of 700 lux in polyethylene terephthalate (PET) bottles with varying light transmittance to monitor the changes in the vitamin A, B₂ and D₃ contents over a storage period of 12 weeks at 23°C. Milk packed in pigmented PET bottles with the lowest light transmittance, which was stored in the dark under the same experimental conditions, served as the ‘control’ sample. In clear PET bottles, a reduction of 93% of the initial content was observed for vitamin A and 66% for vitamin D₃, while the vitamin B₂ content was completely degraded. In all pigmented PET bottles, the vitamin retention was only slightly higher; the losses ranged between 70 and 90% for vitamin A, between 63 and 95% for vitamin B₂, and between 35 and 65% for vitamin D₃ depending on the pigmentation level. In the dark‐stored ‘control’ sample, a 16% loss could be observed for vitamin A, while the level of vitamins B₂ and D₃ remained almost stable. Copyright © 2008 John Wiley & Sons, Ltd.     

Comparative Evaluation of Certain Excipients and their Binary Blends for Direct Compression Oxytetracycline Hydrochloride Tablets

Abstract

Five direct compression excipients as well as their binary blends in ratios of 1:1, 1:3 and 3:1 were comparatively evaluated to compress oxytetracycline hydrochloride into tablets. With respect to the mechanical properties of the produced tablets, Avicel PH101, Celutab and STAR-x1500 in this order, were the most suitable single excipients for the production. The results showed that the incorporation of a second excipient in the formulation changes the physical standards of the produced antibiotic tablets. It was found that not only the type of the incorporated excipient is effective but also, its concentration in the formula. The investigation proved that Avicel/STAR-x1500 blends in all different ratios followed by some blends of celutab with Avicel or STAR-x1500 were the best blended excipients to produce satisfactory antibiotic tablets.     

Stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE)-acetabular components with α-tocopherol

A stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE) with α-tocopherol (vitamin E) used for endoprostheses can increase its resistance against oxidative degradation remarkably. However, the method used for conventional UHMW-PE of adding α-tocopherol to the UHMW-PE powder before processing can not be applied for crosslinked UHMW-PE, since the α-tocopherol hinders the crosslinking process, which would be accompanied by a heavy degradation of this vitamin. The α-tocopherol has therefore to be added after the crosslinking process. This paper presents two methods for a stabilisation of finished products with α-tocopherol. In method 1, UHMW-PE-cubes (20 × 20 × 20 mm³) were stored in pure α-tocopherol under inert atmosphere at temperatures from 100^∘C to 150^∘C resulting in a high mass fraction of α-tocopherol in the edge zones. For further homogenisation, the cubes were stored in inert atmosphere at temperatures from 160^∘C to 200^∘C. In method 2, supercritical CO₂ was used to incorporate the vitamin into the UHMW-PE. In an autoclave vessel, the cubes were treated with α-tocopherol dissolved in supercritical CO₂ for several hours at temperatures from 100^∘C to 170^∘C. In both cases, the mass fraction of α-tocopherol was detected with the help of a FTIR-microscope. Both methods are well suited to stabilise crosslinked UHMW-PE with α-tocopherol. A stabilisation of the sensitive edge layer as well as a nearly homogenous distribution with varying α-tocopherol content may be realised by varying the process parameters. Using method 2, standard hip cups were stabilized nearly homogeneously with varying mass fraction of α-tocopherol. No oxidation of the UHMW-PE could be detected by infrared spectroscopy (FTIR) and HPLC studies showed a very low degradation of the α-tocopherol for both processes. In partial fulfilment of a Ph.D. (Dr.mont.) thesis at the University of Leoben In partial fulfilment of a diploma thesis at the University of Leoben     

Degradation kinetics of thiamine hydrochloride in directly compressed tablets iii water vapour transmission through free and applied eudragit films

Abstract

Water vapour transmission through free and applied film of four Eudragit resins namely, E₁₀₀, L₁₀₀ and RS₁₀₀ to directly compressed thiamine hydrochloride tablets was investigated. The type of Eudragit film influenced both water vapour transmission and moisture absorption characteristics of the tablets compressed with either single or binary blend of vehicles. The moisture absorption rate constant K_a, for a given batch was found to be a function of vapour pressure, P, and film thickness, L. The relationship between K_a and either of these parameters is exponental and may be expressed as K_a = A exp (x/P) and K_a = K*_a exp (-x*L). In general, film coating with Eudragit resins affected the physical characteristics of the tablets. The rate of drug release, K has an exponentially relationship as K_e K_o exp (-c/L).     

Effect of package light transmittance on the vitamin content of pasteurized whole milk

Pasteurized whole milk (3% fat) was stored under fluorescent light at 8°C in clear 1 litre polyethylene terephthalate (PET) bottles and three variants of pigmented PET bottles with different light transmittance. Changes in the vitamin content were monitored over a period of 10 days. Milk packed in pigmented PET bottles with the lowest light transmittance, which was stored in the dark under the same experimental conditions, served as the ‘control’ sample. Data were obtained for vitamin A (retinol), vitamin B₂ (riboflavin) and vitamin B₁₂ (cobalamin) content. Standard plate counts were determined to ensure an acceptable microbiological status of the pasteurized milk during the sampling period. In clear PET bottles a reduction of 22% of the initial content was observed for vitamin A and 33% for vitamin B₂, while the vitamin B₁₂ content remained almost stable. In all pigmented PET bottles the vitamin retention was significantly higher; the losses were 0–6% for vitamin A and 11–20% for vitamin B₂, depending on the pigmentation level, as compared to 6% for vitamin A and no significant loss for vitamin B₂ in the ‘control’ sample. An impact of the package light transmittance on the vitamin B₁₂ content could not be observed. Copyright © 2006 John Wiley & Sons, Ltd.     

Acid catalytic hydrothermal conversion of carbohydrate biomass into useful substances

Acidic hydrothermal degradation of glucose was examined in the presence of HCl, H₂SO₄, and H₃PO₄ with pH varying from 1.5 to 2.5 and reaction time varying from 1 to 10 min at 523 K, to investigate the effect of different acid catalysts and acid concentration on the production of 5-hydroxymethyl-2-furaldehyde (HMF) and levulinic acid from glucose. At lower acidities of pH 2.5, a considerably higher amount of HMF was produced. The increase in acid concentration accelerated the conversion of HMF to levulinic acid. The order for the production of HMF using the three acids is in the sequence of H₃PO₄ > H₂SO₄ > HCl. On the contrary, the order for production of levulinic acid follows HCl > H₂SO₄ > H₃PO₄. In the experimental conditions used in this study, the highest yield of levulinic acid is about 55%, which was obtained at pH 1.5 for 5 min in the case of HCl as an acid catalyst, and the total highest yields of HMF and levulinic acid are about 50%, which occurred at pH 2.0 for 5 min in the case of H₃PO₄ as an acid catalyst.     

Silicon coating treatment to improve high temperature corrosion resistance of 9%Cr steels

Abstract

A silicon coating process is described which confers good protection on 9% Cr steels and alloys in CO₂ based atmospheres at high temperatures and pressures. The coatings are formed by decomposition of silane at temperatures above 720 K. Protective layers are typically up to 1 μm thick. The optimum coating conditions are discussed. The chemical state of the coatings has been investigated by X-ray photoelectron spectroscopy and has demonstrated the importance of avoiding silicon oxide formation during processing. Corrosion testing has been carried out for extended periods, up to 20 000 h, at temperatures between 753 and 853 K, in a simulated advanced gas cooled reactor gas at 4 MPa pressure. Benefit factors of up to 60 times have been measured for 9% Cr steels. Even higher values have been measured for 9Cr–Fe binary alloy on which a 1 μm coating was sufficient to eliminate significant oxidation over 19 000 h except at the specimen edges. The mechanism of protection is discussed. It is suggested that a silicon surface coating for protecting steels from high temperature corrosion has some advantages over adding silicon to the bulk metal.

MST/1090     

The phase diagram YF3-GdF3

The binary phase diagram YF₃-GdF₃ was studied by differential scanning calorimetry (DSC). Yttrium fluoride and gadolinium fluoride show complete miscibility in all three phases (orthorhombic room temperature phase, trigonal or hexagonal high temperature phase, liquid). The transformations between room temperature and high temperature phases are of first order and occur at 1338.6 K (YF₃) or 1174.8 K (GdF₃). Melting points are 1403.1 K (YF₃) or 1525.7 K (GdF₃), respectively. The c_p(T) curve of GdF₃ shows a λ shaped local maximum at 1333 K that might be related to a further solid phase transformation of second order.     

Tabletting Properties of Musol; A New Direct Compression Vehicle

A new autocompressible vehicle, Musol, obtained by chemical modification of an edible seed polysaccharide was evaluated for direct compression properties, A Hausner ratio of 1,2 and percent compressibility of 16.7 obtained for Musol indicate that it has very good flow properties. Musol showed superiority over Avicel PH 101, USP Fast-Flo lactose, and Encompress when evaluated in terns of flow rake of powders and moisture sorption by both powders and their slugs, Compacts prepared with Musol were found to disintegrate by erosion and therefore did not perform as well as either alginic acid or Ac-disol in 250 mg Sulphadimidine tablets. However, good drug release was obtained from aspirin tablets containing 5% w/w Musol as a dry binder. The t₅₀, t₉₀ and Dissolution efficiency were as good as the values obtained with 5% w/w Avicel PH 101, A 50/50 blend of Musol and Avicel PH 101 surpassed other blends in performance.     

Investigation into The Yellowing on Aging of Sabril® Tablet Cores

Abstract

Uncoated Sabril® tablet cores under long term storage become slightly discolored from the initial white to a yellowish off-white color. In order to ensure the aesthetics of the product, Sabril tablet cores are film coated with an opaque white coating. The nature of this yellowing reaction was of interest even though discolored tablets showed no significant loss of potency on assay. Excipient compatibility studies showed that the vigabatrin active in Sabril mixed with Avicel (microcrystalline cellulose) in the presence of moisture also became off-colored when stressed at elevated temperatures.

The nature of the discoloration in aged Sabril core tablets was investigated. Chromatographic and spectroscopic data indicate that the source of this color comes from the Maillard Reaction between vigabatrin and Avicel which results in a multitude of products analogous to “browning reactions” of food products. A gravimetric determination of the leached colored products from 7 year old Sabril core tablets gave a residue of less than 0.1% relative to vigabatrin. Furthermore, based on spectroscopy, most of this residue was found to be povidone, an excipient in the tablets which was isolated along with the colored substances.

Therefore, the colored products identified in the core of Sabril tablets stored for an extended period of time represent only minor impurities. Their formation through aging arises via the Maillard Reaction and would only constitute a matter of aesthetics. The latter problem is avoided by the currently employed film coating process.

Similar reactions could be predicted for other drugs having amine functional groups if they are formulated with microcrystalline cellulose or reducing sugars.     

Hierarchical Bi2S3 nanoflowers: A novel photocatalyst for enhanced photocatalytic degradation of binary mixture of Rhodamine B and Methylene blue dyes and degradation of mixture of p-nitrophenol and p-chlorophenol

Hierarchical nanostructures of bismuth sulfide (Bi₂S₃) have been synthesized by a facile hydrothermal method. The potentiality of Bi₂S₃ hierarchical nanostructures for the photocatalytic degradation of Rhodamine B (RhB), Methylene blue (MB) and the mixture of RhB-MB organic dyes have been demonstrated and compared with commercial TiO₂ (Degussa P25) sample under visible light illumination. The degradation efficiency of Bi₂S₃ and Degussa P25 is found to be higher in the single as well as in the binary dye solution for MB degradation as compared to RhB degradation. Furthermore, the degradation rate of RhB and MB is enhanced by ～8 times and ～3 times in their binary solution as compared to that in single dye solution. Whereas, Bi₂S₃ has demonstrated ～14 times higher degradation rate of both RhB and MB in their binary solution than that of Degussa P25 for RhB and MB degradation in the binary solution under visible light exposure, respectively. Interestingly, Bi₂S₃ nanostructures has exhibited larger improvement in the degradation efficiency for RhB in its binary solution which is attributed to the faster separation of photogenerated charge carriers due to the proper alignments between the molecular orbits of dyes and band level positions of Bi₂S₃ in RhB-MB-Bi₂S₃ heterogenous system. The photocatalytic degradation study of colourless contaminants, p-chlorophenol (CP), p-nitrophenol (NP) and their mixture (CP-NP) is also investigated in the presence of Bi₂S₃ nanoflowers. Among the phenolic compounds, the degradation rate of NP is observed to be highest in the single solution. However, the degradation rate of both CP and NP is found to decrease in binary mixture solution in comparison to their individual solution. A possible mechanism for the enhanced photodegradation of RhB-MB dye mixture based on the active species trapping experiment has been proposed.     

Equilibria,kinetics and mechanism for the degradation of the cytotoxic compound L-NG-nitroarginine

L-N^G-nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration. This work, for the first time, details a systematic study on the determination of equilibrium K_a constants and the rate law of LNNA degradation. The four K_a values of LNNA were determined to be 1.03, 1.10?×?10^?2, 2.51?×?10^?10, and 1.33?×?10^?13 M. From the kinetic and equilibrium studies, we have shown that the deprotonated form of LNNA is the main form of LNNA that undergoes degradation in aqueous media at room temperature. The rate law of LNNA degradation was found to be first order with respect to OH^? concentration and first order with respect to LNNA^? concentration. The rate constant at 25?°C and 1?atm was determined to be 0.04453 M^?1min^?1. A base catalyzed mechanism of LNNA degradation was proposed based on the kinetic study. The mechanism was found to be very useful in explaining the discrepancies and changes of the rate law at different pH values. It is thus recommended that LNNA should be formulated as a concentrated solution in acidic conditions for maximum chemical stability during storage and be diluted with a basic solution to near physiological pH just before administration.