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It is a well reported fact that large number of drugs coming of the drug discovery pipeline show poor aqueous solubility. Eutectic mixture formation of poorly soluble drugs with hydrophilic carriers has been used to enhance the dissolution rate of such poorly soluble drugs. Eutectic mixtures are solid dispersions where the drug and the carrier are both in crystalline form. The eutectic mixture has a lower melting point than either component. Eutectic mixtures are thermodynamically stable systems. The feasibility of developing a dosage form from an eutectic mixture depends on the phase diagram. Poloxamers are polyoxyethylene-polyoxypropylene-polyoxyethylene block polymers which have surfactant properties. Phase diagram construction and dissolution rate enhancement mechanism in crystalline poloxamer based eutectics has not been reported in pharmaceutical literature. This thesis involved the detailed study of poloxamer 188 (PL 188) based eutectic mixtures. Eutectic mixture formation between PL 188 and drugs with diverse physicochemical properties was proved. Accurate experimental phase diagrams were constructed using solid state characterization techniques and theoretical phase diagrams were predicted using Lacoulonche et al's model. The model was accurate in predicting the phase diagrams of most drugs. Discrepancies were observed in case of drugs showing hydrogen bonding interactions with PL 188. This was confirmed by a blue shift of the carbonyl band using fourier transform infra-red spectroscopy. A unique novel graphical method for estimating the accurate eutectic composition of PL 188 based eutectics with about 50 mg of drug was devised. PL 188 was effective in improving the dissolution rate of a poorly soluble drug ibuprofen in pH 1, 4.5 and 7.2. For the first time a detailed study establishing melting point depression due to eutectic formation as a reason for dissolution enhancement was described. Contrary to expectation it was realized that maximum dissolution rate enhancement takes place at drug ratios well above the eutectic composition. The utility of PL 188 as a eutectic mixture carrier was shown by comparing ketoprofen PL 188 eutectic mixtures with ketoprofen soluplus (glass solutions) and ketoprofen urea solid dispersions(amorphous precipitation in crystalline carrier). The ketoprofen PL 188 eutectic mixtures had better dissolution enhancing effect and physical stability. / Pharmaceutical Sciences

Pharmaceuticals are a group of emerging organic compounds of environmental concern used extensively in human and veterinary medicine. They are continually released into the environment as a result of manufacturing operations and excretion from humans and animals. These compounds enter directly into the municipal sewage systems and into wastewater treatment plants. A large number of important and potentially harmful organic contaminants, such as these pharmaceuticals, are not regulated in drinking and other waters. As a result, conventional technologies at most waste water treatment plants (WWTPs) discharge water that meet regulatory standards, yet are not specifically designed to remove these organic contaminants. Therefore, pharmaceutical compounds and their metabolites remain in discharged effluent and enter into the natural aquatic environment. Concentrations of pharmaceutical residues measured in water are typically reported in the ranges of ug/L to ng/L, which are at least three to four orders of magnitude lower than that required to produce a pharmacological effect. The probability of risks to humans arising from such an acute exposure is unlikely, but the possible effects resulting from life-long exposures and synergistic effects from exposure to many chemicals have yet to be determined. It has been widely reported that pharmaceuticals and their metabolites that enter into the aquatic environment can have a potential harmful effect on the aquatic ecosystem and can reach drinking water sources. This research focuses on non-steroid anti-inflammatory drugs (NSAIDs), a group of pharmaceuticals which are widely used as analgesic, antipyretic and anti-inflammatory agents. NSAIDs are frequently used because they are easily accessible as over the counter medication and are a group of drugs that do not produce addiction, respiratory depression, or drowsiness. There is an incentive for removing NSAIDs and other pharmaceuticals from the aquatic environment. Thus, quantitative evaluation of the fate of pharmaceuticals, proper risk assessment and improvement of the efficiency of WWTPs need sensitive and reliable analytical methods. The purpose of this project was to provide a method for detecting three common NSAIDs, IBF, KTF, and NAP, in purified water with LLE-GC-FID. And, an investigation of UV photolysis, UV/H2O2, and UV/TiO2 AOPs was performed to determine their effectiveness in treating IBF, KTF, and NAP in purified water. All treatment methods were successful in degrading target compounds with a total degradation of 86% or greater after 45 minutes. A liquid-liquid extraction technique using methylene chloride and BSTFA + 1%TMCS derivatizing agent was determined for detecting low concentrations of IBF, KTF, and NAP with calibration curves showing good linearity with all R2 values greater than 0.9880.

Universiẗat, Diss.--Münster, 1999.

Made available in DSpace on 2014-06-11T19:31:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-29Bitstream added on 2014-06-13T18:47:45Z : No. of bitstreams: 1 rodrigues_df_dr_botfmvz.pdf: 854052 bytes, checksum: 13482abb726734afc7f37eeff2bffee7 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Avaliou-se o efeito analgésico de Arnica em comparação à utilização de cetoprofeno, no pós operatório de 50 gatas submetidas à ovariossalpingohisterectomia (OSH). Para tanto, as gatas foram divididas em cinco grupos (n=10) e de forma aleatória os animais foram tratados com 1 ml de Arnica 30DH SC (GA30SC); Arnica 30 DH VO (VO) (GA30VO); Arnica 6 DH VO (GA6VO); 2mg/kg de cetoprofeno SC (GC) na primeira aplicação, e 1mg/Kg nas restantes ou 0,1mg/kg de morfina SC (GM). Após 30 minutos realizou-se a OSH e os animais foram avaliados quanto à sedação e dor pós-operatória, por meio de EAV, ECV e hiperalgesia, pelo limiar mecânico nociceptivo por meio dos monofilamentos de Von Frey. Quando o escore da ECV e EAVID atingiram 33% do valor máximo foi realizado o resgate analgésico administrando-se 0,3 mg/kg de morfina IM. Além das escalas anteriormente citadas também foi observado a ocorrência de emese, defecação, micção, peso e cicatrização. Com exceção dos animais tratados com morfina, não houve incidência de vômito. Não houve diferença significativa entre os grupos na defecação, micção, peso e cicatrização. A hiperalgesia foi observada apenas nos momentos em que a EAVID e ECV ultrapassaram 33%, isto é nos momentos em que foi realizado o resgate analgésico. O cetoprofeno e a morfina foram mais eficazes que a Arnica, não houve diferença entre as dinamizações 6DH e 30DH VO, nem entre as vias SC e oral de administração da Arnica em gatas submetidas à OSH / The analgesic effect of Arnica was compared to ketoprofen in 50 cats undergoing ovariosalpingohysterectomy (OSH). Cats were randomly divided into five groups of same number (n=10). The animals were treated with 1 ml of Arnica montana 30DH subcutaneously (SC) (GA30SC); Arnica montana 30 DH orally (GA30VO); Arnica montana 6 DH orally (GA6VO); 2 mg/kg of ketoprofen SC (GC) or 0.1 mg/kg of morphine SC (GM). Surgery was performed 30 minutes after treatments and the animals were evaluated for sedation and postoperative pain through visual analogue scale (VAS), variable count scale (VCS) and hyperalgesia, measuring the mechanical nociceptive threshold by von Frey monofilaments. When VAS and VCS score reached 33% of the of the maximum, analgesic rescue was performed by administering 0.3 mg/kg of morphine intramuscularly. Occurrence of vomiting, stools, urine output, weight and healing was evaluated in addition to the aforementioned scales. Except for the animals treated with morphine, there was no vomiting. There was no significant difference between groups in the stools, urine output, weight and healing. The hyperalgesia was observed only when the VCS exceeded 33% of the total score, when animals received rescue analgesia, but there were no differences between groups. Ketoprofen and morphine were more effective than Arnica montana for postoperative analgesia in cats undergoing ovariohysterectomy. There was no difference between oral Arnica montana at 6DH and 30DH or subcutaneous and oral administration of Arnica montana in cats undergoing ovariohysterectomy

Class of 2006 Abstract / Objectives: To assess perceived efficacy and patient satisfaction at a single point in time during a course of therapy with a compounded topical formulation containing at least ketoprofen in an anhydrous gel base. Methods: Patients aged 18 and older, currently using one of the topical pain relief compounds of interest obtained from Reed’s Compounding Pharmacy in Tucson, Arizona were recruited and then interviewed (in person or by telephone) for this study. Data collected during patient interviews were recorded on a form designed solely for the purposes of this study. Interview questions pertained to the nature of the participant’s pain, their assessment of their pain both before treatment with the medication of interest and at the time of the interview, frequency and duration of patient use of the pain relief gel, disclosure of any other pain relief medications the patient was using at the time, and their overall satisfaction with the medication. Results: Interviews were conducted with a total of 50 patients with chronic pain conditions representing several different etiologies and anatomical locations. The average pain assessment score at the time of the interview (representing perceived patient pain after use of the topical pain relief compound) was significantly lower than the average before treatment pain assessment score (p<0.001). After treatment with the gel had commenced, perceived pain scores dropped by average of 3.56 units (SD 2.28), or 44%. Increased frequency of application of the topical pain relief gel was not associated with greater pain relief or changes in overall patient satisfaction with the product. A longer duration of use of the topical pain relief was also not associated with greater pain relief or overall patient satisfaction with the product. Whether or not a patient utilized other pain relief medication(s) while undergoing treatment with the topical pain relief gel had no bearing on the assessment of their pain either before use of the gel or at the time of interview. The average overall patient satisfaction with the topical pain relief compound was rated at 6.6 out of a possible 10 units (SD 3.13). Thirty-six patients (72%) rated their satisfaction with the topical medication of interest with a satisfaction score of ≥ 6, 10 patients (20%) rated their satisfaction with a score of 10 (completely satisfied), and 6 patients (12%) rated their satisfaction with a score of 0 (not at all satisfied). It was observed that the lower the perceived pain assessment score at the time of the interview (after using the gel), the greater the patient satisfaction with the product. Additionally, patients were observed to be more satisfied with the product if the difference between their perceived pain assessment scores (before and after) was greater (i.e.: greater patient satisfaction with greater pain relief). Conclusions: Treatment of chronic pain with a topical pain relief compound containing at least ketoprofen in an anhydrous gel base is associated with patient satisfaction and perceived analgesic benefits. During the one-time interview, most patients reported a significant improvement in their pain relief, and the great majority of patients were very satisfied with the compounded topical treatment they received from Reed’s Compounding Pharmacy.

Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids gastrointestinal side effects and concentrates drugs in the intended tissues. An extraction and HPLC method was developed for ketoprofen in skin, fascia and muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride removal of lipids, the aqueous layer was acidified with HCl and back extracted into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S-(-)-α-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen recovery was linear (1-33 μg/g) and was detected in these tissues following in vivo cathodic iontophoresis (160 mA*min). This represents the first non-radioactive method for determination of ketoprofen in tissues following transcutaneous iontophoresis.

<p>Tokom perioda rane laktacije brojni unutra&scaron;nji i<br />spolja&scaron;nji faktori vr&scaron;e uticaj na produktivnost i<br />zdravlje mlečnih krava. Najznačajniji unutra&scaron;nji<br />faktori na početku laktacije su zapaljenski<br />procesi i metabolički stres. S obzirom da su<br />metaboličke i imunolo&scaron;ke promene najče&scaron;ći<br />okidač za nastanak bolesti, neophodno je bilo<br />ispitati da li postoji mogućnost regulisanja ovih<br />promena pomoću nesterodinih antiinflamatornih<br />lekova. Cilj ove doktorske disertacije je bio da<br />se ispita uticaj parenteralne primene<br />ketoprofena na metabolički status, inflamatorne<br />promene, odnos između metaboličkih i<br />inflamatornih promena kod krava posle teljenja,<br />kao i na proizvodnju mleka kod krava u ranoj<br />laktaciji. Za ogled je odabrano 30 krava.<br />Oglednoj grupi od 15 krava je i.m. aplikovan<br />ketoprofen u terapijskoj dozi (3mg/kg telesne<br />mase) tokom tri uzastopna dana nakon teljenja.<br />Kontrolna grupa od 15 krava je predstavljala<br />negativnu kontrolu. Uzorci krvi za analizu su<br />uzimani iz repne vene (vena coccygea) na dan<br />teljenja, u prvoj i drugoj nedelji posle teljenja.<br />Procena inflamacije je vr&scaron;ena na osnovu<br />određivanja koncentracije proteina akutne faze<br />(haptoglobina i fibrinogena) i proinflamatonih<br />citokina (interleukina-1&alpha;, faktora nekroze<br />tumora-alfa i interferona gama), dok je procenametaboličkog statusa vr&scaron;ena na osnovu određivanja vrednosti metaboličkih parametarau svim uzorcima krvnog seruma i u svim nedeljama ogleda. Ketoprofen primenjivan parenteralno kod krava posle teljenja je ublažio metabolički stres, uticao na smanjenje inflamatornih procesa i na smanjnje međusobne povezanosti i uticaja između metaboličkih i inflamatornih promena kod krava posle teljenja u poređenju sa netretiranim kravama, a imao je i pozitivan uticaj na proizvodnju mleka u ranoj laktaciji.</p> / <p>During the period of early lactation numerous<br />internal and external factors influence the health<br />and productivity of dairy cows. The most<br />important internal factors at the beginning of<br />lactation are inflammatory processes and<br />metabolic stress. Since the metabolic and<br />immunologic changes are the most common<br />trigger for the disease, it was necessary to<br />examine whether there is a possibility of<br />regulating these changes by using non-steroidal<br />anti-inflammatory drugs. The aim of this<br />doctoral thesis was to investigate the effect of<br />parenteral administration of ketoprofen in the<br />metabolic status, inflammatory changes, the<br />relationship between metabolic and<br />inflammatory changes in cows after calving and<br />milk production in cows in early lactation. This<br />study included 30 cows. Experimental group of<br />15 cows is treated i.m. ketoprofen administered<br />in a therapeutic dose (3 mg / kg body weight)<br />for three consecutive days after calving. A<br />control group of 15 cows accounted for a<br />negative control. Blood samples for analysis<br />were taken from the tail vein (vena coccygea)<br />on the day of calving, in the first and second<br />week after calving. Evaluation of inflammation<br />was based on the determination of the<br />concentration of acute phase proteins<br />(haptoglobin and fibrinogen) and<br />proinflamatonih cytokines (interleukin-1&alpha;,tumor necrosis factor-alpha and interferongamma),and the evaluation of the metabolic status performed on the basis of determining the value of metabolic parameters in a blood sample serum and in all the weeks of the experiment. Ketoprofen administered parenterally in cows after calving eased metabolic stress, had impact on reducing inflammatory processes and the decrease of interconnection and influence between metabolic and inflammatory changes in cows after calving compared with untreated cows, and had a positive impact on milk production in the early lactation.</p><p>&nbsp;</p>

Controlled release formulations deliver an active ingredient over an extended period of time. It is an ideal dosage form for an active ingredient with a short elimination half-life. An active ingredient with a short elimination half-life would be released in small portions over an extended period of time and thus less frequent administration is necessary and this improve patient compliance. Other advantages of these formulations include: decreased side effects, constant drug levels in the blood, improvement in treatment efficiency and reduction in cost of administration. Controlled release beads are formulated in such a way that the active ingredient is embedded in a matrix of insoluble substance like chitosan; the dissolving drug then has to find its way through the pores of the matrix into the surrounding medium. The chitosan matrix swells to form a gel, the drug then has to first dissolve in the matrix and diffuse through the outer surface into the surrounding medium. Chitosan is a biocompatible, biodegradable polymer of natural origin. It has mucoadhesive properties as well as the ability to manipulate the tight junctions in the epithelium membrane and these properties have qualified chitosan as an effective drug carrier in controlled release dosage forms. The effect of a modern controlled release polymer namely Kollidon® SR in combination with chitosan on drug release was investigated. Ketoprofen was chosen as model drug. Ketoprofen is an anti-inflammatory drug that causes gastrointestinal side effects in conventional dosage forms. Ketoprofen has a short elimination half-life of 2.05 ± 0.58 h and this characteristic makes it an ideal candidate for use in a controlled release formulation. The aim of this study was to achieve controlled release and minimize gastrointestinal effects of ketoprofen with chitosan particles. Kollidon® SR was used as polymer because it exhibits pH independent release characteristics and previous studies have shown potential for this combination. Chitosan beads and chitosan-Kollidon® SR beads, as well as chitosan granules and chitosan-Kollidon® SR granules, were prepared and investigated as potential controlled release formulations. Chitosan beads were prepared through the inotropic gelation method using tripolyphosphate as a cross linking agent. Granules were prepared through wet granulation using 2% v/v acetic acid as the granulating fluid or by dissolving ketoprofen in ethanol and Kollidon® SR in 2-pyrrolidinone and using the solution as granulating fluid. Kollidon® SR was added in concentrations of 0.25, 0.5 and 1% (w/v) in the bead formulations and concentrations of 1, 5 and 10% (w/w) in the granule formulations. The beads and granules were characterised by evaluating the following properties: morphology, drug loading and drug release. Additionally swelling and friability tests were also conducted on the bead formulations. The cross linking times of the bead formulations were varied to investigate the effect of cross linking time on the characteristics of the beads. Chitosan-Kollidon® SR beads showed promising results for controlled release formulations and ketoprofen were released over an extended period of time. Drug loading of the plain chitosan beads was 74.65 ± 0.71% and it was noted that the inclusion of Kollidon® SR in the beads resulted in an increase in drug loading and the formulation containing 1% (w/v) Kollidon® SR, cross linked for 30 minutes had a drug loading of 77.38 ± 0.01%. Drug loading of the beads that were cross linked for a longer time were slightly lower which is an indication that some of the drug might have leached out during cross linking. The degree of swelling was promising with some beads swelling to a degree of 2.5 in phosphate buffer solution pH 5.6. Granules had a drug loading between 81.73 ± 1.53% and 93.30 ± 0.50%. Ketoprofen release from the beads and the granules in PBS pH 7.40 at 37 °C over a period of 6 hours were investigated. The bead formulations were more effective in achieving controlled release and it was noted that the bead formulations that was cross linked for a longer period was more efficient in achieving controlled release. The granules did not form a matrix and were not effective in achieving controlled release. Controlled release of ketoprofen were achieved and the results show potential for chitosan-Kollidon® SR formulations in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Neste trabalho, foi realizado o estudo termoanalítico e a caracterização no estado sólido da interação química entre o cetoprofeno (CET) e alguns compostos orgânicos (benzamida (BA), picolinamida (PA), nicotinamida (NA), isonicotinamida (INA), pirazinamida (PZA), ácido salícílico (SA) e ácido benzoico (BA)), visando a obtenção de cocristais. A mecanoquímica foi utilizada como método de preparação dos compostos sólidos, e os mesmos foram analisados por calorimetria exploratória diferencial (DSC), espectroscopia de infravermelho com transformadas de Fourier (FTIR), e difração de raios X de pó (XRPD). A escolha dos compostostos orgânicos (co-formadores) foi baseada em suas estruturas moleculares, de modo que aqueles selecionados para esse trabalho possuíssem uma estrutura molecular capaz de possibilitar a formação de síntons moleculares adequados à formação dos cocristais desejados. A análise dos resultados obtidos permitiu verificar que, nas condições experimentais utilizadas, todas as misturas estudadas formaram apenas compostos eutéticos. Entretanto, embora os diagramas de fases e os experimentos de DSC, raios X e FTIR tenham confirmado apenas a obtenção de compostos eutéticos entre o cetoprofeno e os co-formadores estudados, o método do contato de Kofler indicou a formação de um cocristal entre o cetoprofeno e nicotinamida. Assim sendo, o trabalho realizado até agora abre portas para investigações futuras, nomeadamente, com relação aos estudos de termomicroscopia relativos aos demais sistemas estudados neste trabalho. / In this work, we performed the thermoanalytical study and characterization at the solid state on the chemical interaction between ketoprofen (CET) and some organic compounds (benzamide (BA), picolinamide (PA), nicotinamide (NA), isonicotinamide (INA), pyrazinamide (PZA), salicylic acid (SA) and benzoic acid (BA)), aimed at obtaining cocrystals. The mechanochemical method was used for the preparation of solid compounds, and they were analyzed by differential scanning calorimetry (DSC), infrared spectroscopy with Fourier transform (FTIR), and X-ray powder difraction (XRPD). The choice of the organic compounds (co-formers) was based on their molecular structures, so that those selected for this work possess a molecular structure able to allow the formation of molecular synthons suitable for cocrystals formation. The analysis of the results has shown that under the experimental conditions used, all systems studied has formed only eutectic compounds. However, although the phase diagrams and DSC experiments, X-ray and FTIR have confirmed obtaining only eutectic compounds between ketoprofen and co-formers studied, the method of contact Kofler has indicated the discovery of a new co-crystal formed between ketoprofen and nicotinamide. Therefore, the work done so far opens the door to future research in particular with regard to thermomicroscopy studies related to other systems studied in this work.