A systematic comparison of four pharmacopoeial methods for measuring powder flowability.

Powder flow is one of the crucial factors affecting several pharmaceutical manufacturing processes. Problems due to insufficient powder flow reduce production process efficiency and cause suboptimum product quality. The U.S. Pharmacopoeia has specified four methods to evaluate the flowability of pharmaceutical powders, including angle of repose (AoR), compressibility index (CI) and Hausner ratio (HR), Flow through an orifice, and shear cell. Comparison within and between those methods with 21 powders (covering a wide range of flowability) was performed in this study. Strong correlation was observed between fixed base cone AoR, and fixed height cone AoR (R2 = 0.939). CI and HR values calculated from a tapped density tester (meeting USP standards), manual tapping, and Geopyc® correlated strongly (R2 > 0.9). AoR, CI/HR, minimum diameter for flowing through an orifice (dmin), and shear cell results generally correlate strongly for materials with flowability worse than Avicel® PH102. Both shear cell and CI/HR methods can reliably distinguish powders exhibiting poor flow. For materials with good flow, the ability to distinguish powders follows the order of AoR ≈ CI/HR > shear cell > dmin. The systematic comparison of the four common methods provides useful information to guide the selection of methods for future powder flow characterization. Given the limitations observed in all four methods, we recommend that multiple techniques should be used, when possible, to more holistically characterize the flowability of a wide range of powders.

Application of co-precipitated glutinous rice starch as a multifunctional excipient in direct compression tablets.

Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.

Complete Cocrystal Formation during Resonant Acoustic Wet Granulation: Effect of Granulation Liquids.

The manufacturing of solid pharmaceutical dosage forms composed of cocrystals requires numerous processes during which there is risk of dissociation into parent molecules. Resonant acoustic wet granulation (RAG) was devised in an effort to complete theophylline-citric acid (THPCIT) cocrystal formation during the granulation process, thereby reducing the number of operations. In addition, the influence of granulation liquid was investigated. A mixture of anhydrous THP (drug), anhydrous CIT (coformer), and hydroxypropyl cellulose (granulating agent) was processed by RAG with water or ethanol as a granulation liquid. The purposes were to (i) form granules using RAG as a breakthrough method; (ii) accomplish the cocrystallization during the integrated unit operation; and (iii) characterize the final solid product (i.e., tablet). The RAG procedure achieved complete cocrystal formation (>99%) and adequately sized granules (d50: >250 µm). The granulation using water (GW) facilitated formation of cocrystal hydrate which were then transformed into anhydrous cocrystal after drying, while the granulation using ethanol (GE) resulted in the formation of anhydrous cocrystal before and after drying. The dissolution of the highly dense GW tablet, which was compressed from granules including fine powder due to the dehydration, was slower than that of the GE tablet.

Evaluation of using spray-dried glutinous rice starch as a direct compression hydrophilic matrix tablet.

BACKGROUND: Our previous study found that spray-dried glutinous rice starch (sGRS) is larger in size, rounder in shape and better in flowability than native GRS. It has the potential to be used for direct compression hydrophilic matrix (HM) tablets. OBJECTIVE: This study aimed to investigate the factors that affect the propranolol release from directly compressed sGRS HM tablets. METHODS: The effects of the amount of sGRS, the compaction pressure and the amount of magnesium stearate on the drug release rate from sGRS directly compressed HM were investigated. In vitro drug releases were performed. The dilution potential of sGRS was investigated. RESULTS: The higher the sGRS content, the slower the release rate of propranolol. The compaction pressure and the amount of magnesium stearate did not significantly affect the release rate of the drug. The sGRS showed plastic deformation under compaction with a dilution potential of 46%. CONCLUSIONS: sGRS can be used as a direct compression HM. The amount of sGRS significantly affected the release rate of the drug from the matrix.

Mechanical strength, structural and hydration properties of ethanol-treated starch tablets and their impact on the release of active ingredients.

Ethanol-treated starch (ETS) shows potentiality to be used for binder of pharmaceutical tablets. This study was aimed to evaluate the mechanical strength, structural and hydration properties of ETS tablets and ETS tablets containing lauric acid and ascorbic acid and their release behavior. ETS was prepared from cassava starch at the temperatures of 80, 90, and 100 °C. The active compounds were entrapped within the ETS tablets by two methods, including dry mixing and ethanol solubilisation. The results indicated that ETS tablets from temperatures of 80 °C showed granular shapes, had high friability and low crushing strength indexes, and dispersed and released active ingredients rapidly upon contact with water. Meanwhile, ETS tablets from temperatures of 90 and 100 °C exhibited non-granular particles, had low friability and high crushing strength indexes. Upon hydration, the tablets of non-granular ETS containing lauric acid eroded gradually and released active ingredients during tablet's erosion, meanwhile ascorbic acid diffused out gradually from the swelled tablets.

Simultaneous quantitative analysis of indomethacin and benzoic acid in gel using ultra-violet-visible spectrophotometry and chemometrics.

BACKGROUND: In order to manufacture pharmaceutical products, real-time monitoring in the manufacturing process is necessary, but large equipment cost is required to achieve it. OBJECTIVE: The aim of this research is to use ultra-violet-visible spectroscopy along with chemometrics procedure to simultaneously carry out quantitative analysis of indomethacin (IMC) and benzoic acid (BA) in the gel during pharmaceutical manufacturing process. METHODS: The gel preparations contained 0.1-1.5% IMC, 0.015-0.225% BA, 2% carbopol® 941 and 95% ethanol solution. The calibration models were constructed using the partial least square regression (PLS). RESULTS: The relationships of the measured and predicted concentrations for both IMC and BA had linear plots. The developed PLS calibration models were used to monitor the IMC and BA concentrations during mixing of the gels by the planetary centrifugal and conventional mixers, respectively. IMC and BA were gradually dispersed, dissolved and completely homogeneous within 30 min by the centrifugal mixer. In contrast, IMC and BA were slowly dispersed, dissolved and completely homogeneous at more than 60 min by the conventional mixer. CONCLUSIONS: The ultra-violet-visible spectrophotometric method couples with multivariate chemometric techniques for quantitative data analysis were successfully applied for the simultaneous determination of major component IMC and trace component BA in the gel.

Evaluation of swelling processes of various natural polymer matrix tablets by X-ray computed tomography and controlled drug release.

BACKGROUND: The swelling properties and the drug-release sustainability of pre-gelatinized starches (𝛼-starch) tablets depend on the polymer characteristics. OBJECTBS: In order to clarify the drug release form, the natural polymers (NPs) were investigated. The relationship between drug release and swelling of natural polymers (NPs), the swelling processes of various starch polymers, were investigated using a drug-release test (DRT) and X-ray computed tomography (XCT). NPs consisting of various starches such as glutinous rice starch (GRS), corn starch (CS), and tapioca starch (TS) were used as additives for sustained drug-release tablets. Tablets consisted of 5% theophylline, 94% 𝛼-starch, and 1% magnesium stearate and were compressed at 6 kN. DRTs were measured in distilled water at 37 °C, and the drug concentrations were measured using UV (271 nm). Swelling ratio (R) profiles of the tablets during DRTs were evaluated based on XCT images. RESULTS: The order of the drug-release rate constant of the tablets was TS < GRS < CS. XCT images of the tablets were measured during the DRTs, and CS, GRS, and TS tablets swelled and showed increased gel-layers, and then finally disintegrated at 6, 9, and 11 h, respectively. CONCLUSION: The relationship between R profile and the % drug release of the tablets differed depending on the kind of NP used.

Rapid identification of oral solid dosage forms of counterfeit pharmaceuticals by discrimination using near-infrared spectroscopy.

BACKGROUND: Since it can take an enormous amount of time and cost to discriminate counterfeit medicines by using conventional methods, counterfeit medicines has been spread in the world markets. OBJECTIVE: The purpose of this study was to develop a rapid and simple analytical method to discriminate counterfeit drugs using near infrared (NIR) spectroscopy. METHODS: Seven types of brand name tablet and generic tablets containing atorvastatin calcium sesquihydrate (AT) preparations were used as simulated counterfeit medicines. NIR spectra of 35 AT tablet products were measured using a diffuse reflection method. RESULTS: The NIR spectral data were analyzed by principal component analysis (PCA). The PCA results suggested that the model had sufficient accuracy to discriminate the 7 types for AT tablets. The NIR spectral data were also analyzed using a soft independent modeling of class analogy (SIMCA) method. Predicting the classification of the AT tablet samples was performed based on all the validated AT tablet data using the SIMCA model, and the probability of classification of 7 types was 100%. The discrimination power spectrum of the SIMCA model indicated significant patterns based on diluents. CONCLUSIONS: The PCA and SIMCA classification of the AT tablets were depended on the major excipient combinations.

Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study.

AIM: This study evaluated the in vitro antibacterial effects of the formulated Punica granatum (PG) gel against Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus casei. MATERIALS AND METHODS: The PG extract was dissolved in water at 500 mg/mL. High performance liquid chromatography (HPLC) was used for identification and quantification of chemical marker punicalagin. Minimum bactericidal concentration (MBC) and time-kill assay (TKA) were investigated. Antibacterial activities of the formulated PG gel, 2% chlorhexidine (CHX) gel and blank gel were tested by measuring the zones of inhibition through agar well diffusion method. RESULTS: The HPLC results showed presence of punicalagin at 2023.58 ± 25.29 pg/mL in the aqueous PG extract and at 0.234% (w/w) in the formulated PG gel. The MBC for S. mutans, S. Sanguinis, and L. casei were 250, 125, and 500 mg/mL respectively. The TKA of 500 mg/mL aqueous PG extract showed total inhibition of S. mutans, S. Sanguinis, and L. casei at 6, 1, and 24 hours contact time respectively. Agar well diffusion revealed that for S. mutans, CHX gel > PG gel > blank gel; for S. sanguinis, CHX gel = PG gel > blank gel; for L. casei, CHX gel > PG gel = blank gel. Comparison of the PG gel potency showed that S. sanguinis = S. mutans > L. casei. CONCLUSION: The PG gel equivalent to 0.234% punicalagin (w/w) inhibited S. mutans and S. sanguinis but not L. casei within 24 hours incubation period and has the potential to be used for caries prevention. HOW TO CITE THIS ARTICLE: Millo G, Juntavee A, Ratanathongkam A, Nualkaew N, Peerapattana J, Chatchiwiwattana S. Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study. Int J Clin Pediatr Dent 2017;10(2):152-157.

Optimization of Adhesive Pastes for Dental Caries Prevention.

Dental caries prevention products available on the market contain only remineralizing agents or antibacterial agents. This study aimed to develop adhesive pastes containing calcium phosphate and α-mangostin for dental caries prevention using the optimization technique. Calcium phosphate was used as a remineralizing agent, and extracted α-mangostin was used as an antibacterial agent. The effect of the independent variables, which were fumed silica, Eudragit® EPO, polyethylene glycol, and ethyl alcohol, on the responses was investigated. The drying time, erosion rate, calcium release rate, and α-mangostin release rate were established as the measured responses. An equation and a model of the relationship were constructed. An optimal formulation was obtained, and its effect on dental caries prevention was investigated using the pH-cycling model. The quadratic equation revealed that the drying time, calcium release rate, and α-mangostin release rate tended to decrease when increasing the fumed silica and decreasing other factors. The erosion rate tended to increase when decreasing Eudragit® EPO and increasing other factors. The observed responses of the optimal adhesive pastes were not significantly different from the predicted responses. This result demonstrated that optimization is an efficient technique in the formulation development of the adhesive pastes. In addition, the optimal adhesive pastes could enhance acid resistance activity to the tooth enamel.

Optimization of metronidazole sustained-release films using D-optimal design.

The aim of this study was to develop sustained-release metronidazole films for periodontal pockets using a computer-aided statistical approach. The studied independent variables were the amount of polycaprolactone, metronidazole, hydroxypropylmethyl cellulose and glyceryl monostearate. The response of interest was the cumulative percentage release of metronidazole at 1, 2, 3, 4 and 5 days. The films were prepared using a melt method. The physicochemical properties and release profiles of the films were investigated. Model validation was also performed. The produced films were thin white sheets with a smooth and glossy surface. Each sheet had an average weight of 9.31 ± 0.10mg. The metronidazole was uniformly dispersed in the film, and the percentage of drug loading was 100.12 ± 4.38%. The thickness of the film was 325 ± 5.27 µm. The puncture strength, % elongation and Young's modulus were 11.58 ± 0.51 N/mm(2), 33.51 ± 3.61%, and 0.347 ± 0.02 1N/mm(2), respectively. The actual drug release profiles of the optimal formulation films were close to the predicted responses. Metronidazole was slowly released from the matrices over a period of at least 5 days. The release mechanism of the films followed Fickian diffusion. This study demonstrates that appropriate D-optimal design and optimization techniques can be successfully used in the development of metronidazole sustained-release films.

Quantitative analysis of α-mangostin in hydrophilic ointment using near-infrared spectroscopy.

The objective of this research was to quantify the α-mangostin content in mangosteen pericarp (MP) ointment as a colloidal dispersion using near-infrared (NIR) spectroscopy. Various concentrations of MP (IP and EP) ointments containing both internal and external pericarps were prepared and the NIR spectra of these ointments were measured. The NIR spectrum of each ointment was correlated with α-mangostin concentration by partial least square (PLS) regression. Validation of the models was performed and their predictive ability was also investigated. The equation and R(2) value for the prediction of α-mangostin concentration in IP ointment were y=0.9843x+0.4441 and 0.9730 and those in EP ointment were y=0.9569x+0.1142 and 0.9136, respectively. The biases of the IP and EP ointment models were 0.23 and 0.00, respectively. The results showed that NIR could be a useful tool for the quality control of herbal medicine in hydrophilic ointment without any sample preparation. It could predict α-mangostin content in hydrophilic ointment at very low concentration with sufficient accuracy.

The Antibacterial Effects of Apacaries Gel on Streptococcus mutans: An in vitro Study.

BACKGROUND: New approaches for chemomechanical caries removal require effective materials with antibacterial properties for removal of infected dentin. Apacaries gel is a newly developed material comprised polyphenol from mangosteen extracts and papain mixed in gel preparation. AIM: This study evaluated the antibacterial effects of Apacaries gel on Streptococcus mutans in vitro. MATERIALS AND METHODS: Mangosteen pericarp powder was extracted. The amount of phenolic compounds was determined using the Folin-Ciocalteu method. The time-kill kinetics were investigated. Mangosteen extract and papain were mixed with gel base to develop Apacaries gel. The inhibition zone of the Apacaries gel was determined using agar well diffusion methods. RESULTS: The mangosteen pericarp extract, which contains α-mangostin, was active against S. mutans strain ATCC25175. The time-kill kinetics curve showed that applying 1 mg/ml of mangosteen extract can reduce S. mutans by 50% within approximately 5 seconds; after this reduction, the bacterial count rapidly dropped to 0 within 60 seconds. Using mangosteen extract and papain mixture gel preparation resulted in a larger inhibition zone than using the mangosteen extract gel or papain gel separately. CONCLUSION: Apacaries gel can effectively inhibit S. mutans strain ATCC25175. Apacaries is capable of S. mutans inhibition better than both mangosteen extract or papain separately. How to cite this article: Juntavee A, Peerapattana J, Ratanathongkam A, Nualkaew N, Chatchiwiwattana S, Treesuwan P. The Antibacterial Effects of Apacaries Gel on Streptococcus mutans: An in vitro Study. Int J Clin Pediatr Dent 2014;7(2):77-81.

Application of NIR spectroscopy for the quality control of mangosteen pericarp powder: quantitative analysis of alpha-mangostin in mangosteen pericarp powder and capsule.

Near-infrared spectroscopy (NIR) was applied to the quantitative analysis of the concentration of alpha-mangostin (aM) in mangosteen pericarp powder (MP). The predicted results from the partial least squares chemometric method of various pretreatment data were compared to obtain the best calibration model. Two different types of containers (transparent capsules and glass vials) filled with the same samples were measured. For MP mixture in vials, the calibration model involving nine principal components (PC) could predict the amount of aM most accurately based on non-pretreatment spectral data. For MP mixture in capsules, the calibration model involving nine PC could predict the amount of aM most accurately based on first-derivative pretreatment spectra. The relationships of the calibration models for both samples had sufficiently linear plots. The standard error of cross-validation for the MP mixture in vials was lower and the R(2) values of validation were higher compared to the MP mixture in capsules. The equation for prediction of the concentration of aM in MP mixtures in vials is y = 0.9775x + 0.0425 with R(2) = 0.9950 and for those in capsules is y = 1.0264x + 0.0126 with R(2) = 0.9898. Both validation results indicated that the concentrations of aM in MP mixtures were predicted with sufficient accuracy and repeatability. NIR can be a useful tool for the quality control of herbal medicine in powder form without any sample preparation. The type and the shape of the container should be considered to obtain more accurate data.

Comparison of Marginal Microleakage of Glass Ionomer Restorations in Primary Molars Prepared by Chemo-mechanical Caries Removal (CMCR), Erbium: Yttrium Aluminum-Garnet (Er:YAG) Laser and Atraumatic Restorative Technique (ART).

BACKGROUND: It is important to emphasize that the aspects of pretreatment techniques, as well as the composition and mechanism of adhesion, may decisively influence the effectiveness of the restorative materials in sealing cavity margins and preventing marginal leakage. AIMS: This study assessed the in vitro influence of surface preparation techniques on the microleakage of glass ionomer restorations in primary teeth. MATERIALS AND METHODS: The study groups were divided into three different techniques: (1) The chemomechanical caries removal (CMCR) method using the Apacaries gel, (2) the erbium:yttrium aluminum-garnet (Er:YAG) laser method and (3) the atraumatic restorative technique (ART). The teeth restored with a glass ionomer restorative material (Fuji IX GP capsule, GC Corporation, Tokyo, Japan). The dye penetration was measured in micrometers using a polarized light microscope and specific computer software. RESULTS: The results showed that the mean microleakage level after was lowest with the CMCR method using Apacaries gel and highest with the Er:YAG laser. There was a statistically significant difference regarding the mean microleakage level between the group with the CMCR method using Apacaries gel and the Er:YAG laser. CONCLUSION: Marginal leakage was significantly higher with preparations made using the Er:YAG laser than with the CMCR method using Apacaries gel and spoon excavator (p < 0.05). How to cite this article: Juntavee A, Juntavee N, Peerapattana J, Nualkaew N, Sutthisawat S. Comparison of Marginal Microleakage of Glass Ionomer Restorations in Primary Molars Prepared by Chemomechanical Caries Removal (CMCR), Erbium: Yttrium Aluminum-Garnet (Er:YAG) Laser and Atraumatic Restorative Technique (ART). Int J Clin Pediatr Dent 2013;6(2):75-79.

The physicochemical properties of a spray dried glutinous rice starch biopolymer.

Glutinous rice starch (GRS) is a biopolymer used widely in the food industry but not at all in the pharmaceutical industry. There are several ways to modify this biopolymer. Physical modification is simple and cheap because it requires no chemicals or biological agents. The aim of this study was to characterize the physicochemical properties of a spray dried glutinous rice starch (SGRS) produced from pregelatinized GRS. The surface morphology changed from an irregular to concave spherical shape as revealed by Scanning Electron Microscopy (SEM). SGRS was almost amorphous as determined by X-ray Diffraction (XRD) spectroscopy. The water molecules became linked through hydrogen bonds to the exposed hydroxyl group of amorphous SGRS as determined by Near Infrared (NIR) spectroscopy. Then, SGRS formed a colloid gel matrix with water and developed a highly viscous gelatinous form as determined using Differential Scanning Calorimetry (DSC) and a stress control type rheometer. In addition, SGRS can swell and produce a gelatinous surface barrier like a hydrophilic matrix biopolymer which controls drug release. Therefore, a novel application of SGRS is as a sustained release modifier for direct compression tablets in the pharmaceutical industry.

Time-controlled pulse-drug release from dry-coated wax matrix tablets for colon drug delivery.

This study aimed to prepare a colon drug delivery system using dry-coated time-controlled disintegration wax matrix tablets. Indomethacin was used as a model drug. Behenic acid and lactose were used as coating materials. The effects of lactose content and pH of the dissolution medium on drug release were investigated. The porosity and the tortuosity of the surface matrix layer were calculated. Four formulations of wax matrices containing different percentages of lactose in the surface layer, i.e. 70, 65, 60 and 55, were prepared. The lag times of indomethacin release from the matrices in 0.05 M phosphate buffer pH 7.4 were 50, 162, 294 and 539 minutes for formulations containing 70, 65, 60 and 55% lactose, respectively. The release of drug from formulations containing lactose in the range of 60-70% in different media, i.e. 0.05 M phosphate buffer pH 7.4, 0.05 M alkaline borate buffer pH 8.5 and in the case of pH changed media from pH 1.3 to pH 7.4, was not different (p=0.1). This implies that the different environment in the gastro-intestinal tract will not affect the release of this delivery device. The required lag time period can be met by varying the amount of lactose.