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The main objective of this research is to develop an immediate release Rupatadine fumarate 10 mg tablets formulation by direct compression, through a Quality by Design approach in Costa Rica. Methods: According to a Quality by Design approach; Target Product Profile, Quality Target Product Profile and the Critical Quality Attributes were defined. In the preformulation study, compatibility tests were carried out between the raw materials. The Critical Material Attributes were established using Quality Risk Management. Three formulation prototypes were prepared by direct compression and its Critical Process Parameters were defined. The analysis of the prototypes was realized in terms of organoleptic properties, identification, potency, content uniformity, dissolution, disintegration, friability and loss by drying. Results: All the prototypes showed a white or slightly pink surface, potency between 90.0 – 110.0% of the labeling, an acceptance value for the content uniformity lower than the specification (AV < 15), the dissolved amount of active pharmaceutical ingredient was greater than 85.0 % at 30 minutes, friability less than 1.0 %, a disintegration time less than 15 minutes and moisture content less than 2.0%. Conclusions: The approaching of a Quality by Design model to the current development allowed to obtain satisfactory results in the three formulation prototypes. The excipients to be used can be lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, pregelatinized starch, magnesium stearate, stearic acid and PVP K-30. Universidad de Costa Rica/[]/UCR/Costa Rica UCR::Vicerrectoría de Docencia::Salud::Facultad de Farmacia UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones Farmacéuticas (INIFAR)

Antivenoms or antitoxins have been effectively used for more than a century. During this time, these products have always proven to be highly effective in the treatment of infections and envenomations. However, antivenoms did not exhibit good safety results in their initial applications. After many improvements, antivenoms have substantially better safety profiles but still have some side effects. Due to the occurrence of adverse reactions, the practice of using premedication with the intent to decrease side effects has become accepted or mandatory in many countries. The drugs used for premedication belong to the histamine H1 antagonist, glucocorticoid and catecholamine groups. Currently, this practice is being questioned due to low or controversial efficacies in clinical assays. In this article, we discuss the causes of adverse reactions, the mechanisms of drugs that block the undesired effects and the results obtained in clinical trials. Although these three families of drugs could have positive effects on reducing adverse reactions, only adrenaline has demonstrated positive results in clinical assays.

Hedychium spicatum (Ham-ex-Smith), known as Shati in Ayurvedic classics, is documented for the treatment of cough, hiccough, fever and asthma. The present study includes the evaluation of aqueous and ethanolic extracts of the dried rhizome of H. spicatum for anti-histaminic and ulcer-protective activities in guinea pig (GP), anti-inflammatory and analgesic activities in rat and acute toxicity in mouse. The extracts were administered orally, daily as suspension, in 1% carboxymethyl cellulose either for 7 days in GP studies or 60 min before or just before experiment in rats and mice. An initial dose-dependent anti-histaminic action of both the extracts (100, 200 and 400 mg/ kg) was performed against histamine-induced bronchospasm in GPs. The 200 mg/ kg dose of aqueous and ethanolic extracts was selected both in GP and rat for further studies. GPs treated with aqueous and ethanolic extracts showed gastric ulcer protection against histamine-induced gastric ulcer compared with the control group. Both the extracts also showed an anti-inflammatory effect against carrageenan-induced paw edema in rats from 1 h onwards, and this was maximum at 3 h. Analgesic effect was determined by using hot plate and tail flick tests in rats, and both the extracts at 200 mg/kg showed a significant increase in the latent period from 30 min onwards till 120 min of their study period. Both the extracts did not show any toxic effect like increased motor activity, salivation, clonic convulsion, coma and death in mice even at the 2000 mg/kg dose (nearly 10 times of the optimal effective dose), indicating the safety of the extracts. The result confirms the indigenous use of this plant in respiratory disorders.

Pharmacokinetic (PK) models are mathematical tools that allow simulating drug concentration levels in the blood prior to real administration. These models can have countless applications in new drug development and clinical activities. Concerning clinical practice, a factor limiting the widespread use of PK models is the difficulty to carry out personalized PK predictions. This article proposes a methodology to individualize a physiologically based pharmacokinetic model for applications in therapeutic drug monitoring. In order to personalize the model, it is necessary to determine patient-specific model parameters. Few drug concentration measures in the blood allow evaluating the parameter values by performing a nonlinear regression between the generalized model predictions and the measured drug concentrations of a specific patient. The resulting model, comprising an ordinary differential equations system and a set of personal model parameters, allows forecasting personalized drug concentration levels with good precision. This model can be of real help in supporting pharmacological treatments for chronic patients administered with low therapeutic-index drugs that hinder possible toxicity risks.

Resumen: El insomnio es una patología muy frecuente en edad pediátrica (30% en niños menores de 5 años) que ocasiona una grave repercusión cognitiva, emocional y en el aprendizaje junto con una importante comorbilidad médica y afectación de la calidad de vida del niño y la familia. La formación de los pediatras en el diagnóstico y el tratamiento del mismo suele ser deficitaria. Por todo ello, se presenta el documento de consenso sobre el manejo del insomnio en la infancia y la adolescencia elaborado por representantes de la Asociación Española de Pediatría, la Sociedad Española de Sueño, la Sociedad Española de Pediatría Extrahospitalaria y de Atención Primaria, la Sociedad Española de Medicina de la Adolescencia, la Sociedad Española de Psiquiatría Infantil y la Sociedad Española de Neurología Pediátrica. Este grupo recomienda que el diagnóstico debe ser clínico y solo en los casos dudosos o en que sea necesario un diagnóstico diferencial serán necesarias pruebas complementarias. Asimismo el tratamiento se debe basar principalmente en terapias cognitivo-conductuales y en una modificación de los hábitos de sueño. El uso de medicamentos y sustancias para facilitar el sueño es elevado, aunque no existen guías clínicas que lo apoyen. Abstract: Insomnia is very common during childhood (30% of children under 5), and causes a serious cognitive and emotional consequence in learning, as well as significant medical comorbidity. It also affects the quality of life, not only of the child, but also of the whole family. Paediatrician training in its diagnosis and treatment is usually poor. For this reason a consensus document is presented on the management of insomnia in children and adolescents. This has been developed by members of the Spanish Paediatrics Association, the Spanish Sleep Society, the Spanish Society of Paediatric Outpatient and Primary Care, the Spanish Adolescent Medicine Society, the Spanish Child and Adolescent Society, and the Spanish Paediatric Neurology Society. The group suggests that diagnosis must be clinical and complementary tests will only be required in doubtful cases or when a differential diagnosis is needed. Likewise, treatment should be mainly based on cognitive-behavioural therapy and the modification of sleeping habits. Using medicines and other substances to make the sleep easier is currently quite common, even although there are no clinical guidelines to support this.

Bauhinia racemosa Lam. (Caesalpiniaceae) leaves have been used in the treatment of asthma traditionally and we therefore undertook this study to scientifically validate its benefit in asthma using suitable animal models. Antihistaminic principles are known to be useful in the treatment of asthma; hence, in the present work, the antihistaminic activity of an ethanol extract of B. racemosa (at a dose of 50 mg/kg, i.p.) was assessed using clonidine-induced catalepsy and haloperidol-induced catalepsy in Swiss albino mice. The results showed that the ethanol extract inhibits clonidine-induced catalepsy but there is no effect on haloperidol-induced catalepsy. This suggests that the inhibition is through an antihistaminic action and that there is no role of dopamine. Hence, we concluded that the ethanol extract has significant antihistaminic activity. The polar constituents in the ethanol extract of leaves of B. racemosa may be responsible for the antihistaminic activity and B. racemosa may therefore have a role in the treatment of asthma.

Bir α2 adrenoreseptör agonisti olan xylazine uygulamasına bağlı olarak köpeklerde bradikardi, hipotansiyon, hipopnea, bulantı ve kusma gibi yan etkiler görülebilmektedir. Bu çalışma xylazine hydrochloride’e bağlı oluşan bulantı ve kusmanın önlenmesinde bir H1 reseptör antagonisti olan mepyramine maleate’ın etkinliğinin araştırılması amacıyla yapıldı. Çalışmada 30 köpek kullanıldı ve köpekler 10’arlı 3 gruba ayrıldı. Çalışmada antihistaminik uygulamasının yapıldığı an 0. dakika kabul edilerek, birinci guruptakilere 1 mg/kg, ikinci gruptakilere 2 mg/kg dozda intramuskuler (i.m.) mepyramine ve üçüncü gruptakilere ise eşit miktarda i.m. serum fizyolojik enjeksiyonu yapıldı. Bütün köpeklere bu enjeksiyonlardan 20 dakika sonra 2,2 mg/kg dozda i.m. xylazine enjekte edildi. Xylazine enjeksiyonundan sonra birinci ve ikinci gruptakilerden birer köpek kusarken üçüncü gruptakilerden sekiz köpek kustu. Üçüncü gruptakilerden dokuzunda bulantı gözlenirken, birinci grupta 2 ve ikinci grupta 3 köpekte bulantı saptandı. Birinci ve ikinci gruplarda mepyramine uygulamasından sonraki 40., 60. ve 80. dakikalarda (xylazine uygulamasından sonraki 20., 40. ve 60. dakikalar) pulzasyon ve respirasyon önemli (P

Radioreceptor assays can be a useful tool for systematic toxicological analysis in that they can be applied for the detection of an entire pharmacological class of drugs. In the present paper procedures for radioreceptor assays for benzodiazepines, anticholinergics and antihistaminics have been described in detail. The development of the assay for antihistaminics in urine is given in order to illustrate the prerequisites for these types of assays with regard to the incubation conditions. In part 2 the applicability of the three assays for systematic toxicological analysis will be evaluated on the basis of testing a large number of urine samples after administration of a selected number of drugs to healthy volunteers and patients.

In this paper the applicability ot radioreceptor assays tor systematic toxicological analysis will be evaluated on a theoretical basis as well as on the basis of the outcomes of the analysis of a large number of urine samples collected after administration of a selected number of drugs to healthy volunteers and patients. Many drugs and other substances of toxicological relevance exert their action through an interaction with one or more receptor (sub)types. Whether the number of persons are using particular drugs intentionally of unintentionally, radioreceptor assays can be a useful tool for systematic toxicological analysis in that they can be applied to the identification ot entire pharmacological classes of substances as well as pharmacologically active metabolites. In part 1 of this paper detailed procedures for radioreceptor assays for benzodiazepines, anticholinergics and antihistaminics have Deen described in detail in order to illustrate not only the potentials but also the limitations of assay conditions. Fifteen drugs were administered to patients and volunteers and urine samples were collected and determined with the three radioreceptor assays. The results ot this study underline the theoretical applicability ot receptor assays in systematic toxicological analysis though sample pretreatment procedures may contribute to an improvement in sensitivity and applicability to other biofluids.

Gihan S Labib1,2 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Objectives: Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will.Materials and methods: Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability.Results: All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets.Conclusion: Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. Keywords: antihistaminic, effervescent tablets, 2-hydroxypropyl-β-cyclodextrin, mannitol, taste masking&nbsp

The aim of present research was to develop a fast releasing oral polymeric film, with good mechanical properties, instant disintegration and dissolution, producing an acceptable taste when placed on tongue. Solvent casting method was used to prepare oral films. Levocetirizine dihydrochloride, an antihistaminic was incorporated to relieve the symptoms of allergic rhinitis. The polymers selected were HPMC E 15 and PVA. Propylene glycol was the plasticizers used. Nine batches of films with drug were prepared using different combinations of polymers and plasticizer concentration. The resultant films were evaluated for weight variation, content uniformity, folding endurance, thickness, surface pH, in vitro disintegration and in vitro dissolution. The optimized films which disintegrated in less than 30 sec, releasing 85-98% of drug within 2 minutes. The percentage release was varying with concentration of plasticizer and polymer. The films made with HPMC: PVA (1:2) released 96% of drug in 1 min, which was the best release amongst all.