Ibuprofen is a non-steroidal anti-inflammatory drug whose pharmaceutical activity can be improved by particle size reduction. Micronization of ibuprofen using rapid expansion of supercritical solution (RESS) process was investigated in this study. Thanks to high solubility of ibuprofen in supercritical CO2,extraction temperature and pressure in RESS process are considered a bit more than critical point of SC-CO2. The unprocessed and processed ibuprofen powders were characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fouriertransform infrared spectrophotometry (FT-IR).FT-IR analysis and XRD pattern of processed ibuprofen showed that the degree of crystallinity was reducedwithout any chemical structural change.DSC analysis showed a 3.8 K decrease in the melting point from that of bulk ibuprofen.Also, the RESS processing of ibuprofen leads tospherical particles in the range of 50 to200 nmas reflected by SEM observations.
Keywords:Rapid Expansion of Supercritical Fluid, Ibuprofen, Drug Delivery, Crystallinity, Micronization.
Introduction
40% of the new drugs developed in pharmaceutical industry are lipophilic and due to their poor water solubilityfails to reach market [1]. Some of them are: ibuprofen, carbamazepine, miconazole, and acetaminophen. Hence, there always is an urgent need to improve dissolution rate and oral bioavailability of poor water soluble drugs. There are various techniques available to improve the solubility of these drugs such as pH adjustment, microemulsion, self-emulsifying drug delivery systems, particle size reduction, and supercritical fluid (SCF) process [2].
Supercritical fluid technology is a relatively new technique for micro...
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...e length on particle size of product and also compared the dissolution kinetics of raw ibuprofen and micronized ibuprofen produced by the RESS process [22]. Results show that pre-expansion pressure and nozzle length have no effect on particle size but an increase in spraying distance result in a slight decrease in particle size. Also, dissolution rate of micronized ibuprofen is enhanced as the particle size decreases.
The rapid expansion of supercritical solution was applied to the size reduction of ibuprofen particles in this research and effect of extraction pressure and temperature have been studied on particle size and morphology. Also, the aim of the present study isthe characterization of physicochemical properties of micronized ibuprofen particles in details.These include: surface properties, crystallinity, morphology, thermal behavior and chemical structure.
Craig, D. Q. (2002). Pharmaceutical Applications of Micro-Thermal Analysis. Journal of Pharmaceutical Science, 91(5), 1201-1213.
However, low HLB surfactants may also be an important component of oral lipid-based formulation by behaving as a coupling agent for the high HLB surfactants and the lipophilic solvent components, as well as contributing to solubilization by remaining associated with the lipophilic solvent post-dispersion. Moreover, using a blend of high and low HLB surfactants may also lead to more rapid dispersion and finer emulsion droplet size upon addition to an aqueous phase [36, 48, 49, 51–55]. Thus, in this study, we decided to mix Tween 80 (high HLB value) with Carbitol (low HLB value) to identify the most effective combination emulsifying with three chosen oils. The size of the emulsion droplets decreased as the HLB value of surfactant mixture reached the required HLB (Table 2). In the case of soybean oil, the smallest size was 277 ± 2.49 nm obtained at 20:80 (v/v) ratio of Tween 80:Carbitol). In the cases of ethyl oleate (Tween 80:Carbitol, 90:10, v/v) and IPM (Tween 80:Carbitol, 60:40), the smallest droplet sizes were 2.9 ± 0.170 and 10.5 ± 0.596 nm, respectively. These results show that the combination of Tween 80 and Carbitol had extremely good emulsifying ability, resulting in a fine emulsion in the cases of using ethyl oleate and IPM oil. The results of the visual test (Fig. 1) are parallel to the results of droplet size measurements. The combinations that had a smaller droplet size of 100
The aspirin crystals were packed into 3 small capillary tubes to ensure that they are compressed so as to prevent any air gaps. Subsequently, the aspirin crystals that are in the 3 capillary tubes are placed into the melting apparatus and the temperature range was recorded. Since the range is quite far from the theoretical value of 140°C, aspirin's purity attained was low due to impurities present. One potential reason is because of the swift cooling. When the aspirin is left to cool, the crystal lattices will form too rapidly which will surround other molecules thus making the aspirin impure. Another reason could be because the recrystallized aspirin has not dry completely and there might me left over solvent that will affect the temperature range of the aspirin.
Aspirin is also known as Acetylsalicylic acid. It is composed of nine Carbon atoms, eight Hydrogen atoms, and four Oxygen atoms. There are many chemical properties to it. The melting point of aspirin is about one hundred and thirty-five degrees Celsius and the boiling point is one hundred and forty degrees Celsius. It has a density of 1.35 grams per milliliter and the molar mass is 180,160 g/mol (1). This means that the molecule is relatively dense. There is more weight than there is volume. Aspirin is described as odorless and colorless to where the color is white. It looks like a crystal-line powder at room temperature. It is a relatively stable molecule that should be stored at room temperature (2).
In this case study, our concern goes for the chitosan nanoparticles; firstly nanoparticles are able to adsorb and/or encapsulate a drug, thus protecting it against chemical and enzymatic degradation. Furthermore the encapsulated drug may be prevented from crystallization, thus forming a solid solution. Depending on drug solubility in the carrier, a drug load varying from only a few percent up to 50%] Secondly, chitosan is ...
Memories of World War II play a very important role in the world today, especially in East Asia. These memories are not simple but complicated factors that created many of the controversial issues that exist today. Two of the main issues that revolve around East Asia are the Nanjing Massacre and the comfort women issue. People have debated over the truth of the Nanjing Massacre and the comfort women issue, and people on different sides have not come to an agreement on the historical facts. Daqing Yang’s “The Malleable and the Contested, Joshua Fogel’s “Nanjing Atrocity and Chinese Historical Memory ” discusses the issues in detail, and Chungmoo Choi’s “The Politics of War Memories toward Healing”.
Solubility is based on the highest-dose strength of an immediate release product. A drug is considered highly soluble when the highest dose strength is soluble in 250 mL or less of aqueous media over the pH range of 1 to 7.5. The volume estimate of 250 mL is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water. A drug substance is considered highly permeable when the extent of intestinal absorption is determined to be 90% or higher. Otherwise, the drug substance is considered to be poorly permeable. (Yu et al., 2002)
Solubility is defined as the maximum amount of a substance that will dissolve in a given amount of another substance at constant temperature and pressure. Solubility is typically expressed in terms of maximum volume or mass of the solute that dissolve in a given volume or mass of a solvent. Traditionally the equilibrium solubility at a given pH and temperature is determined by the shake flask method. According to this method the compound is added in surplus to a certain medium and shaken at a predetermined time. The saturation is confirmed by observation of the presence of un-dissolved material. Saturation can also be reached if the solvent and excess solute is heated and then allowed to cool to the given temperature. After filtration of the
Size and stability: Liquid formulation can be bulky, difficult to transport and store.1 During storage under the stated conditions, it’s necessary that oral solutions are not subject to precipitation, fast sedimentation, caking or formation of lump.2 They have poor stability compare to solid dosage form formulation due to hydrolysis.1 Therefore, it’s important to optimize the active ingredient stability in liquid formulation including those prepared from powder or granules.2
The term nanocarriers includes a wide range of different nanosized drug delivery systems. The oldest and at the same time the most clinically established nanocarriers are liposomes, spheres composed of an aqueous core surrounded by one or more concentric lipid bilayers. They are suited for the encapsulation of both hydrophillic and hydrophobic drugs, respectively in the aqueous core and whitin the lipid membrane (Hafner e.a. 2014). Liposomes increase thus the solubility of hydrophobic compounds, they enable trapping of drug molecules with a high potency, they reduce systemic side effects and toxicity and they attenuate drug clearance (Riehemann e.a. 2009)
This paper describes the separation and isolation of the three active components of Excedrin. The three components of aspirin, acetaminophen, and caffeine were separated using the technique of acid-base extraction with K2HPO4 and KOH being the bases and HCl as the acid. Distillation was also performed on the ether layer to extract the caffeine. One week later, crystals from the K2HPO4 and KOH solutions were acquired via vacuum filtration. Due to the ether evaporating, crystals from the ether did not need to be filtered. Thin Layer Chromatography (TLC) was then performed on the K2HPO4 crystals, the KOH crystals, the ether crystals, the K2HPO4 liquid solution, and the KOH solution. The TLC determined the K2HPO4 crystals as aspirin, the KOH crystals
The aims of this study were to measure the physicochemical properties of miconazole nitrate (MCZ : a brand-name (MCZ-A) and three generic (MCZ-B, -C, and -D)) creams, to conduct human sensory testing of those creams. The flattening, viscoelasticity, and water content of each cream were measured and each cream was subjected to near-infrared (NIR) absorption spectroscopy and sensory testing. The yield value was calculated based on measured flattening and was 734.8 dynes/cm2 for MCZ-A, 1198.9 dynes/cm2 for MCZ-B, 461.3 dynes/cm2 for MCZ-C, and 3112.3 dynes/cm2 for MCZ-D. Measurement of viscoelasticity and viscosity revealed that MCZ-C had a smaller tanδ than the other 3 creams at 25ºC. NIR absorption spectroscopy revealed that MCZ-A had the highest absorption peak due to hydroxyl groups, followed by MCZ-C, -B, and then -D. Measurement of water content revealed that MCZ-A had a water content of 65.9%, MCZ-B, -C, and -D had a water content of around 56.3%. Human sensory testing revealed differences between MCZ-A and MCZ-C and between MCZ-B and MCZ-D in terms of spreadability and feel. These findings indicate that differences in water and oil content and emulsification resulted in the creams having different physical properties, such as flattening, internal structure, and dynamic viscoelasticity. NIR absorption spectroscopy, which allows non-destructive measurement of a sample’s physicochemical properties, and measurement of viscoelasticity and viscosity, which allows measurement of a sample’s dynamic viscoelasticity, revealed differences in the physical properties of creams.
The conical vial was placed in a small beaker and allowed to cool to room temperature. The mixture was Cooled thoroughly in an ice bath for 15-20 minutes and crystals collected by vacuum filtration on a Hirsch funnel. The vial was rinsed with about 5 mL of ice water and transferred into to the Hirsch funnel and again washed with two additional 5mL portions of ice water. Crystals were dried for 5-10 minutes by allowing air to be drawn through them while they remained on the Hirsch funnel. The product was transferred to a watch glass plate and allow the crystals to dry in air. Crude acetaminophen product was weighed and set aside a small sample for a melting point determination and a color comparison after the next step. Calculation of the percentage yield of crude acetaminophen (MW = 151.2). was done and recorded in the lab notebook.
Part C. Ibuprofen consists of covalently-bonded carbon, hydrogen, and oxygen atoms. Two CH3 molecules are single-bonded to a CH molecule. The CH molecule is bonded to a carbon atom that forms a 6-sided ring of carbon atoms. Another CH molecule is single-bonded to a carbon atom on the other side of the ring. There are 3 double bonds inside the rings between carbon atoms. On the right, another CH3 molecule and a COOH molecule are both single bonded to the CH molecule.
In modern medicine industry, biological techniques are widely used in the production of pharmaceuticals. Pharmaceutical biotechnology products are the medical products extracted from native biological sources and used for therapeutic or in vivo diagnostic purposes. Normally, these biological products include proteins, such as antibodies, and nucleic acids, such as DNA and RNA. However, as the high sensitivity to external environment, the stability of biopharmaceutical products are easily affected by some physicochemical factors, biological factors, etc. As a result, during the process of manufacturing, packaging and storage, biopharmaceutical products have a high risk of degradation which could lead to significantly negative influences