17 research outputs found
Penentuan Waktu Tanam Bawang Merah(allium Ascalonicum L) Berdasarkan Neraca Air Lahan Di Kecamatan Petang, Kabupaten Badung
The timing of planting shallots (Allium ascalonicum L). Based on Soil Water Balance Land in districts Petang, order to determine the water balance Land in Districts Petang, knowing Water balance land and crop water needs shallots so that can determine the time of planting shallots right in District Petang. This study uses the average precipitation, humidity, solar radiation, wind speed and temperature. From the average data of climate is then used to calculate potential evapotranspiration (ETo) using CropWat application for windows. ETo of calculation is used to analyze the soil water balance, using the method of Thornthwaite and Mather, (1957). The results showed that potential evapotranspiration in the evening during the year amounted to 1643 mm with actual evapotranspiration (ETA) of 1591 mm. Periods of water surplus land in the evening lasted for seven months in November - in May. Water re-charging period (recharge) to the land which has been experiencing drought occurred in November, the best planting time for the shallots in Petang is December. With increasing water needs in accordance with the increasing age of the plant, which peaked in mid-stage season stage. Thus the plants can utilize the water contained in the soil for the growth of vegetative and generative growth of these plants do not require much water and harvest is expected in February
Emergence of 3D Printed Dosage Forms: Opportunities and Challenges
The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored.
This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry
Structural basis for the transformation pathways of the sodium naproxen anhydrate-hydrate system
Crystal structures are presented for two dihydrate polymorphs (DH-I and DH-II) of the non-steroidal anti-inflammatory drug sodium (S)-naproxen. The structure of DH-I is determined from twinned single crystals obtained by solution crystallization. DH-II is obtained by solid-state routes, and its structure is derived using powder X-ray diffraction, solid-state 13C and 23Na MAS NMR, and molecular modelling. The validity of both structures is supported by dispersion-corrected density functional theory (DFT-D) calculations. The structures of DH-I and DH-II, and in particular their relationships to the monohydrate (MH) and anhydrate (AH) structures, provide a basis to rationalize the observed transformation pathways in the sodium (S)-naproxen anhydrate–hydrate system. All structures contain Na+/carboxylate/H2O sections, alternating with sections containing the naproxen molecules. The structure of DH-I is essentially identical to MH in the naproxen region, containing face-to-face arrangements of the naphthalene rings, whereas the structure of DH-II is comparable to AH in the naproxen region, containing edge-to-face arrangements of the naphthalene rings. This structural similarity permits topotactic transformation between AH and DH-II, and between MH and DH-I, but requires re-organization of the naproxen molecules for transformation between any other pair of structures. The topotactic pathways dominate at room temperature or below, while the non-topotactic pathways become active at higher temperatures. Thermochemical data for the dehydration processes are rationalized in the light of this new structural information
Properties of the Sodium Naproxen-Lactose-Tetrahydrate Co-Crystal upon Processing and Storage
Co-crystals and co-amorphous systems are two strategies to improve the physical properties of an active pharmaceutical ingredient and, thus, have recently gained considerable interest both in academia and the pharmaceutical industry. In this study, the behavior of the recently identified sodium naproxen-lactose-tetrahydrate co-crystal and the co-amorphous mixture of sodium, naproxen, and lactose was investigated. The structure of the co-crystal is described using single-crystal X-ray diffraction. The structural analysis revealed a monoclinic lattice, space group P21, with the asymmetric unit containing one molecule of lactose, one of naproxen, sodium, and four water molecules. Upon heating, it was observed that the co-crystal transforms into a co-amorphous system due to the loss of its crystalline bound water. Dehydration and co-amorphization were studied using synchrotron X-ray radiation and thermogravimetric analysis (TGA). Subsequently, different processing techniques (ball milling, spray drying, and dehydration) were used to prepare the co-amorphous mixture of sodium, naproxen, and lactose. X-ray powder diffraction (XRPD) revealed the amorphous nature of the mixtures after preparation. Differential scanning calorimetry (DSC) analysis showed that the blends were single-phase co-amorphous systems as indicated by a single glass transition temperature. The samples were subsequently tested for physical stability under dry (silica gel at 25 and 40 °C) and humid conditions (25 °C/75% RH). The co-amorphous samples stored at 25 °C/75% RH quickly recrystallized into the co-crystalline state. On the other hand, the samples stored under dry conditions remained physically stable after five months of storage, except the ball milled sample stored at 40 °C which showed signs of recrystallization. Under these dry conditions, however, the ball-milled co-amorphous blend crystallized into the individual crystalline components
Dehydration of Nitrofurantoin Monohydrate during Melt Extrusion
Hot melt extrusion
is important for the development of advanced
pharmaceutical dosage forms. In this study, the dehydration of nitrofurantoin
monohydrate during melt extrusion below the expected dehydration temperature
has been investigated. The influence of process time, temperature,
and drug/polymer ratio on the solid form of the drug compound was
studied using drug/polymer physical mixtures with thermogravimetric
analysis (TGA), differential scanning calorimetry (DSC), X-ray powder
diffraction, rheometry, and hot-stage microscopy and compared with
data generated from the extruded products. Extensive dehydration of
nitrofurantoin monohydrate was surprisingly observed at extrusion
temperatures as low as 70 °C in contrast with TGA and DSC analysis
of the pure drug indicating dehydration onset at around 90 °C.
This was related to shear induced solution-mediated transformation,
where nitrofurantoin dissolved into the molten polymer and rapidly
recrystallized as nitrofurantoin anhydrate, as well as simultaneous
solid–solid transformation. In conclusion, these types of complex
interactions may cause unexpected solid form transformations of the
drug in a melt-based drug product and therefore need to be considered
during the drug development process
Interpreting the Disordered Crystal Structure of Sodium Naproxen Tetrahydrate
The crystal structure of the tetrahydrate
of the active pharmaceutical
ingredient sodium naproxen is examined using single-crystal X-ray
diffraction, supported by <sup>13</sup>C and <sup>23</sup>Na solid-state
NMR. The structure has previously been reported to be a heminonahydrate,
Na<sup>+</sup>(naproxen<sup>–</sup>)·4.5H<sub>2</sub>O.
The average structure in space group <i>C</i>2 contains
layers of naproxen molecules that are ordered, except for two orientations
of the carboxyl groups, and Na<sup>+</sup>/H<sub>2</sub>O regions
that exhibit complex disorder. The atomic positions in the disordered
regions are interpreted as NaÂ(H<sub>2</sub>O)<sub>6</sub> octahedra,
alternately sharing edges and faces to define 1-D coordination polymers
with translational periodicity twice that of the <i>b</i> axis in the average <i>C</i>2 structure. There is also
one noncoordinated H<sub>2</sub>O molecule per two naproxen molecules,
giving an overall formula of {Na<sub>2</sub>(H<sub>2</sub>O)<sub>7</sub>}<sup>2+</sup>(naproxen<sup>–</sup>)<sub>2</sub>(H<sub>2</sub>O). Two resonances seen for the naproxen methyl group in <sup>13</sup>C CP/MAS SS-NMR are accounted for by the presence of two orientations
along the doubled <i>b</i> axis for the carboxyl group.
A single resonance in the <sup>23</sup>Na SS-NMR is consistent with
local 2<sub>1</sub>/<i>m</i> symmetry in the Na<sup>+</sup>/H<sub>2</sub>O regions. The single-crystal X-ray diffraction pattern
contains diffuse rods in positions consistent with the doubled <i>b</i> axis, indicating a disordered stacking sequence for the
Na<sup>+</sup>/H<sub>2</sub>O sections
Exploring the Solid-Form Landscape of Pharmaceutical Hydrates: Transformation Pathways of the Sodium Naproxen Anhydrate-Hydrate System
Strong intermolecular ring current influence on 1H chemical shifts in two crystalline forms of naproxen : a combined solid-state NMR and DFT study
The anhydrous crystalline forms of Naproxen [(S)-(+)-2-(6-methoxy-2-naphthyl)propionic acid], (NAPRO-A) and its sodium salt (NAPRO-S), widely used anti-inflammatory drugs, have been investigated by means of 1D and 2D MAS NMR and density functional theory (DFT) based calculations. From calculations, 1D 13C CP MAS and 1H CRAMPS and 2D 1H–13C MAS-J-HMQC, refocused INEPT, FSLG-HETCOR, and 1H–1H DQ-CRAMPS solid-state NMR experiments, 1H and 13C resonances have been fully assigned for NAPRO-A and -S. In the case of NAPRO-S, all of the nuclei belonging to the two inequivalent molecules of the asymmetric cell gave rise to distinct signals, which could be completely assigned. Interesting intermolecular ring current effects on 1H chemical shifts have been experimentally observed for the two samples, even if with significant differences between the two cases. The measured and calculated proton chemical shift values showed a very good agreement for both NAPRO-A and -S, allowing us to correlate the different ring current effects with the crystal structures. The comparison between the proton chemical shifts calculated in the crystal structures and in vacuo allowed us to confirm the mainly intermolecular character of the ring current effects and to quantify them