Regarding the impact of modern drilling fluids on the environment, it is recommended that everyone must pay attention to these, these are directly related to the human living environment. The oil drilling fluid penetrates into the formation with potassium formate, and the flow resistance is large, which not only inhibits the hydration, dispersion and expansion of the clay, prevents the formation from shrinking, but also does not interfere with the electrical measurement. It has light corrosion and avoids pollution to the oil layer. How to distinguish genuine and fake potassium formate for high quality oil drilling fluid?
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When potassium formate is used in oil drilling fluid, it is generally selected to purchase solids, which is convenient for transportation and more convenient for the preparation of drilling fluid system. Taking potassium formate solid as an example, how to distinguish:
1. The solid potassium formate is white crystal, easy to absorb moisture, and has reducibility. (Chuandong Chemical Group has ensured that potassium formate does not cause any problems in the preparation of drilling fluid systems. When potassium formate is shipped from the factory, no anti-caking agent is added and vacuum packaging is used.) It should be noted that some anti-caking agent may be used. There are other substances in it, which can not meet the requirements of drilling use.
2. The potassium formate aqueous solution is a colorless transparent liquid, the specific gravity of the saturated solution is 1.58 g/cm3, the saturation concentration of potassium formate can reach 76%, and it dissolves quickly. Some impurities will appear if the saturated potassium formate solution is not reached.
3. The content of high quality potassium formate (solid) &#;96%. Not to mention the content, can you use it with confidence even if you can't reach the basic quality indicators?
4. The solubility of high quality potassium formate per 100 ml of water at different temperatures: 313g/10 &#;; 337g/20 &#;; 361g/30 &#;; 398g/40 &#; 471g/60 &#;; 580g/80 &#;; 658g/90 &#;.
5. Potassium formate drilling fluid is a kind of inorganic brine drilling fluid system. It is a non-toxic and easily biodegradable drilling fluid. There is no pungent odor when distinguishing its true and false.
For the oil drilling industry, chemical methods are mostly used. The main role in drilling and completion fluids is potassium ions, which can be completely dissociated. When the same amount is added, the effective K concentration is higher than that of potassium chloride, and there is no pollution of anionic chloride. The surface tension of the filtrate is significantly greater than that of potassium chloride drilling. In the completion fluid system, the flow resistance into the formation is large, which not only inhibits the hydration, dispersion and expansion of the clay, prevents the formation from shrinking, but also does not interfere with the electrical measurement. It has light corrosion and avoids pollution to the oil layer. Therefore, when purchasing potassium formate, you must find a formal company to avoid unnecessary losses.
The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.
This review will address various criteria for the selection of salt forms, as well as suitable examples for each category. Inclusion of all of the examples for each criterion will be beyond the scope of this review; therefore, only a few representative examples are included. It should be noted that various textbooks have been published addressing the salt forms of API; the focus of the majority of the literature is the enhancement of API solubility through salt formation. This review is unique, and aims at offering a succinct report on the salt selection criteria based on the chemical, pharmaceutical, biological, and economical applications of different salt formulations.
The suitability of a candidate for salt selection is determined by the physical and chemical properties of the API; different counterions can be utilized to address one or more shortcomings of the API. The prediction of a salt&#;s qualitative and/or quantitative properties based on the counterion used is an important research area. Several studies have described a link between salt properties and the counterions used [ 3 , 4 , 5 , 6 , 7 , 8 ]. While predictions can be made with some degree of accuracy, there is no reliable way to accurately investigate salt properties based on the counterion used. Currently, a wide range of validated counterions is available to prepare the salts of APIs ( ) [ 9 ]. One important criterion in the selection of counterions is to employ agents that have been previously used in FDA-approved drugs, and are thereby generally recognized as safe (GRAS) [ 7 ].
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The specific salts of active pharmaceutical ingredients (APIs) are often formed to achieve desirable formulation properties. Although addressing poor aqueous solubility is one of the most important reasons to employ a salt formation, pharmaceutical companies also use the formation of unique salt products to commonly address other physicochemical and biological concerns such as stability, toxicity, poor absorption, and issues related to manufacturing processes. The importance of salts is indicated by approximately 50% of the United States Food and Drug Administration (US FDA) approvals consisting of APIs in the salt form [ 1 ]. Moreover, half of the top 200 prescription drugs in the United States consist of pharmaceutical salts [ 2 ]. The choice of the appropriate salt form is dictated by various factors. The formation of potentially marketable salt requires concerted efforts and a thorough understanding of the physical and chemical characteristics of the API and counterions that are used. A rational decision tree approach should be followed for the selection of the best salt in the most economical way. Furthermore, all of the necessary testing should be performed in the early phases of the drug development process in order to minimize failures. Salts can significantly alter physical/chemical properties of an API so much so that it can expedite the drug development process.
The presence of acidic or basic functional groups is an essential requirement for the formation of salts. A majority of the APIs discovered are suitable candidates for salt formation during drug development, since they are either weakly acidic or weakly basic in nature. Salt screening begins with the characterization of acidic or basic functional groups. Depending on the presence of these groups and pharmaceutical needs, a potential counterion can be selected. Low molecular weight bases and acids have higher chances of being a liquid with a low melting point. Salt formation can be employed to augment their melting points and convert and maintain the solid state. For example, Bozigian et al. reported that compound NBI-, which is an investigational compound for the treatment of insomnia, was a crystalline, free base with a low melting point (64 °C) [10]. One of the important pharmaceutical requirements for this compound was to develop a salt that possessed a higher melting point. Since weakly basic drugs require acidic counterions to form ionic bonds, 14 acids were selected as possible counterions. Since the low melting point was one of the concerns for this drug, initial approaches to characterize salt forms included differential scanning calorimetry (DSC), which is an important tool for determining the melting point as well as crystallinity, solvates, and presence or absence of the polymorphs. They were able to successfully find the salt form of NBI- by focusing on the chemistry of the drug [10].
The selection of a counterion is based on the pKa rule, which takes into account the degree of ionization of the acidic or basic functional groups that are present in the drug [11]. According to the pKa rule, when the pKa difference between an acid and base is greater than two or three, salt formation is expected [11,12]. Ideally, for basic drugs, the pKa should be at least two pH units higher than the pKa of the counterion, and for acidic drugs, the pKa of the drug should be at least two pH units lower than the pKa of the counterion chosen. This difference ensures strong binding energy between the opposite ionic species so that the complexes formed will not readily break down into individual species when not required. For example, phenytoin is a well-known acidic drug with a pKa value of 8.4; however, it has limited solubility. One important pharmaceutical property for this drug that needed to be addressed was improving its aqueous solubility. Due to the acidic nature of the drug, basic counterions with pKa values >10.4 were likely to form pharmaceutically acceptable salts. Therefore, a strong basic counterion such as NaOH was needed to form a desirable salt of phenytoin. Weakly basic counterions would not be able to form salts with phenytoin, since these counterions would not be able to raise the pH above the required pHmax value of 11 [13].
Salt formation is a well-utilized technique to increase the aqueous solubility of a drug. However, hydrophobic salt approaches are sometimes considered to increase the lipophilicity of a drug molecule [14,15]. The decrease in aqueous solubility has been found to be a useful approach to provide greater chemical stability, particularly at high humidity and high temperature. One well-known example is the formation of sulfate as well as hydrophobic salts of xilobam. The sulfate salt of this drug is completely ionized. In fact, it has been found that the presence of aryl groups in the sulfate counterion for this drug protected the base from getting easily hydrolyzed in the presence of high humidity and high temperatures. The formation of hydrophobic salts allows pharmaceutical companies to prepare more stable drugs without affecting their bioavailability [16]. Salt formation leads to increased lipophilicity as a result of the neutralization of the overall electrostatic charge, thereby enhancing the membrane permeability of hydrophilic molecules. As shown in , Sarveiya et al. correlated the effect of several counterions of ibuprofen on log P value and membrane absorption [17], and clearly demonstrated the effects of the different counterions on these properties.
Hygroscopicity is defined as the ability of a material to absorb and retain moisture at various temperatures and humidity conditions. Low hygroscopicity is a preferred characteristic of drugs, as the moisture content can significantly affect stability. Based on the extent of water uptake, APIs can be classified as non-hygroscopic, slightly hygroscopic, and hygroscopic solids [18]. A non-hygroscopic substance can take up moisture from a humid environment, which in turn can alter the mechanical and solubility properties, affecting the performance of a drug. Readily hydrolyzable drugs are more easily degraded due to the presence of water and pH alterations in the microenvironment of the salt. Thus, hygroscopicity needs to be carefully monitored when designing a salt form of a drug. For example, the salts of mineral acids tend to be very polar, leading to increased hygroscopicity and low microenvironmental pH. These factors can affect the stability of some drugs due to a consequential increase in the rate of hydrolysis [19].
A salt with the associated water of crystallization is considered as a hydrate form. These forms have water molecule(s) in the crystalline lattice of the API. Hydrate forms of APIs are quite common; it is estimated that approximately one-third of APIs can form hydrates if exposed to the conditions that are conducive for hydrate formation [20]. Pharmaceutical hydrates are formed when the API comes in contact with water during crystallization, lyophilization, wet granulation, aqueous film coating, spray drying, and storage [21]. If a hydrate is exposed to a dry environment, it can lose the water of crystallization to attain a lower state of hydration or an anhydrous form. The exchange of water between drug and excipients such as starch or cellulose can also affect the solubility and mechanical properties of a drug product [22,23]. Water molecules in pharmaceutical hydrates influence the internal energy, thermodynamic activity, hygroscopicity, solubility, dissolution rate, and stability [23]. Therefore, understanding the hydrate form is crucial in order to better understand these properties and address significant issues if the need arises.
Polymorphism is the ability of a solid compound to exist in more than one crystalline form. Most drugs exhibit structural polymorphism or multiple crystalline forms. In order for a molecule to develop into a potential drug, the existence of a stable polymorph or a suitable pseudopolymorph needs to be established. The polymorphs (or pseudopolymorphs) of drugs show different chemical stability; it is generally observed that a more thermodynamically stable polymorph is more chemically stable than a metastable polymorph [24]. The optimized orientation of molecules, hydrogen bonds, and non-hydrogen bonds in the crystal lattice play an important role in imparting thermodynamic stability to crystal structures. Even small changes in the crystal packing may lead to significant differences in the chemical reactivity of the two polymorphs of the same drug [24]. Between the crystalline form and amorphous forms of the same drug, the amorphous form is less stable due to the lack of a three dimensional crystal structure, free volume, and greater molecular mobility [24]. The amorphous form of penicillin G was shown to be less stable than the crystalline sodium and potassium salts [25]. There are several examples of drug polymorphism&#;s effects on the pharmaceutical fate of the drug. It is beyond the intended scope of this review to address all of the examples. However, it is worthwhile to mention the polymorphism of ritonavir (Norvir®), the discovery of which served as a wake-up call for the pharmaceutical companies. Ritonavir is an antiviral drug marketed by Abbott Laboratories in in the form of semisolid gel capsules for the treatment of acquired immunodeficiency syndrome (AIDS) [26]. The capsules contained the only known crystal form, Form I, which was discovered during the development process. However, in , a new and significantly less soluble polymorph of ritonavir precipitated in the semisolid gel capsules [27,28], which became known as Form II. This form demonstrated a significantly lower solubility in hydroalcoholic solutions than the marketed Form I [28]. The manufacturing of ritonavir semisolid capsules formulation was comprised of a hydroalcoholic solution of the drug, which was found to be saturated with Form II. The sudden appearance and dominance of this less soluble form made the formulation unmanufacturable [27], and also affected the storage of Norvir® oral solution at refrigeration conditions, since lower storage temperatures led to the crystallization of Form II [27]. These factors, along with limited inventory, led to the withdrawal of the drug by Abbot Laboratories, leaving tens of thousands of AIDS patients around the world without medication [26]. Ritonavir was reformulated and approved in before being placed on the market; Abbot lost revenue of over US $250 million in the process [26]. Therefore, understanding salt formulations and their correlation to polymorphism early in drug development is imperative to minimize drug failures at later stages of drug development.
Acidic or basic counterions can alter the pH of the microenvironment in liquid dosage forms. In turn, changes in pH can influence the reactivity of an API with excipients, and can lead to either the improved stability or degradation of the API. Undesirable interactions can generate significant impurities in a drug product [29].
For example, amlodipine is a free base that was initially chosen for developing a maleate salt. However, the presence of maleic acid changed the microenvironment of the drug product, and this alteration led to the formation of the aspartic acid derivative (UK-) by Michael addition, as shown in . This degradation product was found to have different biological activity, and therefore, amlodipine maleate was found to be unsuitable for further development. Although such reactions could be minimized by the careful selection of excipients and by avoiding alkaline conditions [30], besylate (benzenesulfonate) was chosen to be the suitable salt form with significantly fewer problems [12]. This example clearly demonstrates how drug stability can be adversely affected if a counterion is not carefully chosen.
Open in a separate windowSalt formation approaches have widely been utilized to increase solubility, and therefore, the dissolution rate of a drug. It is one of the most common methods to increase the solubility of weakly acidic and basic drugs. Hydrochloride, mesylate, hydrobromide, acetate, and fumarate are the most common counterions that are used for basic chemical entities in the past 20 years [31], while sodium, calcium, and potassium continue to be the most common counterions for weakly acidic drugs. Increases in aqueous solubility have been achieved by most of these counterions. Slater et al. studied the feasibility of salt formation for RPR, having a pKa of 5.3 and an intrinsic free base solubility of 10 µg/mL [32]. The poor aqueous solubility yielded poor bioavailability in animals. While all of the salt forms (hydrochloride, hydrobromide, methanesulfonate, mesylate, and camphorsulfonate) increased the solubility of the parent drug, mesylate salt consistently produced a higher solubility of 39 mg/mL at 25 °C. Other factors such as hygroscopicity, clean polymorphic profile, particle size, and flow properties were also considered, and all of these factors favored the formation of a mesylate salt for further development [32]. This shows that the selection of a suitable counterion should not be an isolated approach that focuses on one consideration at a time, but should instead be a holistic approach, incorporating additional relevant considerations simultaneously.
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