Trazodone Hydrochloride Research Articles

Pharmacokinetics and Bioequivalence Evaluation of Trazodone Hydrochloride Sustained-Release Tablets in Healthy Chinese Volunteers.

The aim of this study was to investigate the pharmacokinetics, bioequivalence, and safety of generic trazodone hydrochloride sustained-release tablet and its reference listed product in healthy Chinese subjects. An open, randomized, single-dose, and 2-period crossover study was involved under fasting and fed conditions, with a 7-day washout period. A single oral dose of 150mg of 2 trazodone hydrochloride sustained-release tablets was administered to 84 healthy volunteers, with 36 in the fasting group and 48 consuming a high-fat diet, respectively. The plasma concentrations of trazodone were analyzed using a liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were obtained from concentration-time profiles. The geometric mean ratio with 90% confidence intervals of the maximum trazodone concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the bioequivalence acceptance criteria (80%-125%) under fasting and fed conditions, which indicated that the test and reference formulations were bioequivalent. Compared with the fasting study, the concomitant administration of trazodone with a high-fat diet had a negligible influence on the drug pharmacokinetic behavior. Adverse events were recorded, and no serious adverse events were observed during either fasting or fed conditions. Trazodone has proven to have an acceptable safety profile in the Chinese population, with bioequivalence successfully established under both fasting and fed conditions.

EFEITOS DE FÁRMACOS PSICOTRÓPICOS NO TRATAMENTO DE DISTÚRBIOS COMPORTAMENTAIS EM CÃES (CANIS FAMILIARIS)

With the strengthening of human-animal interaction and the scientific recognition of sentience, there has been a significant increase in the perception of atypical behaviors in companion animals, as observed by legal guardians and veterinarians. In general terms, such changes occur due to excessive humanization, stress, fear, or inappropriate environments, leading to variations in temperament, emotional dependency, and/or inhibition of species-specific natural behaviors. The class of psychotropic drugs offers pharmacological treatment for the mental state of these animals by modulating neurotransmitters such as serotonin and dopamine. The objective of this study was to evaluate the pharmacological impact of psychotropic drugs on the social development and emotional resilience of these animals, in conjunction with behavioral therapy. For this purpose, domestic dogs (Canis familiaris) diagnosed with compulsive disorders secondary to other behavioral dysfunctions were treated with trazodone hydrochloride (Group 1) and extracts from Psilocybe cubensis mushrooms (Group 2), and compared to conventional treatment with fluoxetine hydrochloride. The animals were diagnosed and evaluated using questionnaires aimed at diagnosing and monitoring the evolution of treatment, based on the literature referenced in this study. Atypical behaviors associated with primary and secondary disorders were mitigated or eliminated in Group 1 (n=4), Group 2 (n=4), and the conventional treatment group. However, fluoxetine hydrochloride showed a reduction in appetite as a side effect.

Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

Statistical Design Approach for Optimizing the Spectrofluorimetric Method for Quantifying Trazodone Hydrochloride

Statistical Design Approach for Optimizing the Spectrofluorimetric Method for Quantifying Trazodone Hydrochloride

Development and Evaluation of Trazodone Hydrochloride Tablets for Oral Drug Delivery Technology

Development and Evaluation of Trazodone Hydrochloride Tablets for Oral Drug Delivery Technology

Influence of Genetic Polymorphisms on the Pharmacokinetics of Trazodone Hydrochloride: a Scoping Review and Future Perspective.

Trazodone hydrochloride is an antidepressant used in clinical practice. As a substrate of cytochrome P450 enzymes that is vulnerable to P-glycoprotein transport, several factors can alter its plasma concentration, and hence, dose adjustment may be required. The aim of this scoping review was to identify genetic polymorphisms that influence the pharmacokinetics of trazodone hydrochloride. A literature search was performed using PubMed, PubMed Central, BVS/BIREME, EBSCOhost, Web of Science, Embase, Cochrane Library, and Medline databases for studies published until August 2021. The search strategy was based on the following keywords: Trazodone OR "m-chlorophenyl piperazine" AND "Pharmacogenetics" OR "Genetics" OR "Cytochrome P-450 Enzyme System" OR "Polymorphism, Single Nucleotide" OR "Polymorphism, Genetic." The search retrieved 684 candidate articles; 307 duplicates were eliminated. In total, 377 articles were eligible for the first screen. However, only four met the eligibility criteria, and 12 polymorphisms in five different genes (CYP2D6, CYP1A2, CYP3A4, CYP3A5, and ABCB1). Notably, only C3435T ABCB1 influenced the pharmacokinetics of trazodone hydrochloride. Individuals with the T/T genotype had lower area under the curve, half-life, and maximum concentration values with a higher clearance rate. Polymorphisms in CYP450 do not appear to directly influence the pharmacokinetics of trazodone hydrochloride or its metabolites. Genetic polymorphisms in ABCB1, in contrast, seem to have an important effect on the pharmacokinetics of trazodone hydrochloride by enhancing drug metabolism and elimination.

Attempting to Increase the Effectiveness of the Antidepressant Trazodone Hydrochloride Drug Using π-Acceptors.

Major depressive disorder is a prevalent mood illness that is mildly heritable. Cases with the highest familial risk had recurrence and onset at a young age. Trazodone hydrochloride is an antidepressant medicine that affects the chemical messengers in the brain known as neurotransmitters, which include acetylcholine, norepinephrine, dopamine, and serotonin. In the present research, in solid and liquid phases, the 1:1 charge-transfer complexes between trazodone hydrochloride (TZD) and six different π-acceptors were synthesized and investigated using different microscopic techniques. The relation of dative ion pairs [TZD+, A−], where A is the acceptor, was inferred via intermolecular charge-transfer complexes. Additionally, a molecular docking examination was utilized to compare the interactions of protein receptors (serotonin-6BQH) with the TZD alone or in combination with the six distinct acceptor charge-transfer complexes. To refine the docking results acquired from AutoDock Vina and to better examine the molecular mechanisms of receptor-ligand interactions, a 100 ns run of molecular dynamics simulation was used. All the results obtained in this study prove that the 2,6-dichloroquinone-4-chloroimide (DCQ)/TZD complex interacts with serotonin receptors more efficiently than reactant donor TZD only and that [(TZD)(DCQ)]-serotonin has the highest binding energy value of all π-acceptor complexes.

Design and Development of Gastro-retentive Drug Delivery System for Trazodone Hydrochloride: a Promising Alternative to Innovator's Controlled-Release Tablet.

Trazodone hydrochloride (TZN) is a serotonin reuptake inhibitor that treats a major depressive disorder. It exhibits a short plasma half-life of 4.1 h and shows pH-dependent solubility. Above its pKa (6.74), solubility of TZN is very low, affecting its dissolution in the lower part of GIT. Hence, the present work aimed to develop gastro-retentive floating tablet of TZN. Central composite design was employed to optimize the formulation. Formulation variables like the concentration of HPMC-K100M, Polyox WSR 303 Leo, and sodium bicarbonate were evaluated for the responses like floating lag time and drug release. X-ray imaging study was performed on rabbits to determine the in vivo gastric retention of the optimized formulation. The accelerated stability study was conducted on optimized tablets as per ICH guidelines. Floating lag time and f2 value of the optimized formulation were found to be 2.51±0.02 min and 62.79, respectively. X-ray imaging studies in rabbits determined the in vivo gastro retention time. After 12 h of administration, tablet remained in the gastric region, indicating better retentive power. Accelerated stability studies showed sufficient formulation stability even after 3 months of storage. All these studies depict that the floating gastro-retentive system could be used as an alternative to the innovator formulation.

Are There Differences in the Homogeneity of the Parts of Tablets Obtained after Subdivision?-A Preliminary Assessment Using an X-ray Microtomography.

Aim: The study aimed to analyze the weight and homogeneity of the parts of tablets containing carbamazepine and tablets with trazodone hydrochloride, obtained after subdivision with a kitchen knife. X-ray microtomography was used for homogeneity analysis. Methods: 30 tablets with carbamazepine and 30 tablets with trazodone hydrochloride were analyzed in terms of weight uniformity after subdivision. Then, seven tablets of each type were analyzed using an X-ray microtomography (Phoenix vǀtomeǀx, General Electric). The absorption of X-rays by an object is proportional to its density. In turn, measurement of the density of the analyzed object in a microtomographic image is the grayscale level. Based on the correlation between the grayscale value and the reference density, from the calibration phantom, we were able to determine the density of any area of the tablet’s scan. Results: During the subdivision, the weight loss exceeded 3% for two carbamazepine tablets, while for trazodone tablets, none lost more than 3%, which is the limit recommended by Food and Drug Administration (FDA). As to the density of the tablets resulting from the microtomographic analysis, two of the whole tablets containing trazodone hydrochloride had a significantly higher density than the remainder (p < 0.001). Similarly, some differences in density were observed in the analysis of the density of tablets of carbamazepine (p = 0.008). Parts of one of the analyzed tablets with trazodone obtained after subdivision differed in terms of pixel brightness, thus density. On the other hand, the uniform density was observed for parts of the split tablets containing carbamazepine. Conclusions: Parts of the trazodone hydrochloride tablets obtained after subdivision differed in terms of homogeneity and weight. Microtomographic methods may be an interesting and useful method for evaluating the uniformity of compounds in solid dosage forms.

The effect of preanaesthetic oral trazodone hydrochloride on the induction dose of propofol: a preliminary retrospective study

ObjectiveTo determine whether the administration of trazodone to dogs 2 hours prior to radiotherapy treatment reduced the dose of propofol required to induce anaesthesia. Study designRetrospective, crossover, case-matched study. AnimalsRecords of 30 client-owned dogs. MethodsAnaesthetic records from all dogs undergoing weekly radiotherapy treatment between January 2020 and December 2020 were retrospectively assessed. All dogs were premedicated with 10 μg kg–1 alfentanil and 12 μg kg–1 atropine intravenously (IV) and anaesthesia was induced with IV propofol. In part 1, the propofol induction dose was compared between anaesthetics when trazodone was administered prior to the anaesthetic (T) versus not (NT). For part 2, control dogs not administered trazodone during the treatment course were case-matched based on bodyweight and tumour location and type. The propofol induction dose was compared between the first (C1) and last (C2) anaesthetic to identify the effects of confounding factors. A Wilcoxon signed-rank test for repeated measurements was performed to identify any significant differences in the propofol induction dose between NT and T in the study dogs and between C1 and C2 in the control dogs. ResultsIn part 1, 15 study dogs that were administered trazodone prior to at least one anaesthetic were identified. A significant difference in propofol induction dose between groups NT and T was identified [3.3 (2.1–7.4) and 2.0 (1.5–5.0) mg kg–1, respectively; p = 0.003]. In part 2, 15 dogs were case-matched to the study cohort. The dose of propofol administered did not differ between the first and last anaesthetic [2.5 (1.6–6.4) and 2.6 (1.9–8.9) mg kg–1, respectively; p = 0.638]. Conclusions and clinical relevancePreanaesthetic trazodone administration reduced the induction dose of propofol compared to when it was not administered to dogs following premedication with IV atropine and alfentanil.

Тразодона сукцинат — новые возможности фармакологической коррекции ситуационных поведенческих отклонений у собак и кошек

Currently, the interest of veterinarians and owners in the pharmacological correction of situational behavioral disorders in companion animals has increased significantly. To quickly correct deviant behavior in dogs and cats, veterinarians use some of the psychotropic drugs used in humane medicine, in particular, trazodone, an antidepressant antagonist / serotonin reuptake inhibitor.&#x0D; &#x0D; Based on the analysis of literature sources, data on the history of creation and pharmacological properties, assessment of the safety and efficacy of drugs based on trazodone hydrochloride in behavioral medicine of small pets are provided.&#x0D; The data on the prerequisites for the development, pharmaco-toxicological and clinical evaluation of a new drug for the modification of abnormal behavior in dogs and cats, Express Uspokoin® tablets based on trazodone succinate, which, with a high efficiency of the target action, made it possible to achieve the absence of side effects and significantly increase the tolerance of the dosage form by animals, are analyzed. compared with preparations based on trazodone hydrochloride.

FORMULATION DEVELOPMENT AND EVALUATION OF MATRIX TABLET TRAZODONE HYDROCHLORIDE USING NATURAL POLYMER

Increased complications and costs of marketing of innovative drugs focused greater attention to the development of sustained release (SR) or controlled release (CR) drug delivery systems. Trazodone Hydrochloride (TRZ) is a well-known chemical compound that is used as an antidepressant that belongs to a selective serotonin reuptake inhibitor (SARI). The objective of present work was to develop and evaluated oral sustained release matrix tablet of TRZ. Pre-compression parameters were evaluated. The tablets were evaluated for post-compression parameters such as thickness, hardness, average weight, friability and In vitro release studies. No interactions were observed between TRZ and excipients from the Fourier transform infrared spectroscopy. The present research work was successful in improving the efficacy TRZ oral therapy as the drug release was extended for 12 hours thus reducing dosing frequency thereby improving patient compliance. The study also revealed the applicability of HPMC K-15, Gaur gum and PVP K30 as rate-controlling polymers in matrix tablets. The hydrophilic matrix of HPMC alone cannot control the release TRZ effective for 12 h while when combined with guar gum, may slow down the release of the drug and therefore, can be successfully employed for the formulation of matrix tablets SR. It may be concluded from the study that; the optimized formulation F-8 was shown maximum drug release 99.12 % in 12 h of dissolution. The release kinetic data of formulation F-8 shown first order release kinetics (R2 = 0.980).

Comparison of Medication Prescribing Before and After the COVID-19 Pandemic Among Nursing Home Residents in Ontario, Canada

COVID-19 has had devastating effects on the health and well-being of older adult residents and health care professionals in nursing homes. Uncertainty about the associated consequences of these adverse effects on the use of medications common to this care setting remains. To examine the association between the COVID-19 pandemic and prescription medication changes among nursing home residents. This population-based cohort study with an interrupted time-series analysis used linked health administrative data bases for residents of all nursing homes (N = 630) in Ontario, Canada. During the observation period, residents were divided into consecutive weekly cohorts. The first observation week was March 5 to 11, 2017; the last observation week was September 20 to 26, 2020. Onset of the COVID-19 pandemic on March 1, 2020. Weekly proportion of residents dispensed antipsychotics, benzodiazepines, antidepressants, anticonvulsants, opioids, antibiotics, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors. Autoregressive integrated moving average models with step and ramp intervention functions tested for level and slope changes in weekly medication use after the onset of the pandemic and were fit on prepandemic data for projected trends. Across study years, the annual cohort size ranged from 75 850 to 76 549 residents (mean [SD] age, 83.4 [10.8] years; mean proportion of women, 68.9%). A significant increased slope change in the weekly proportion of residents who were dispensed antipsychotics (parameter estimate [β] = 0.051; standard error [SE] = 0.010; P < .001), benzodiazepines (β = 0.026; SE = 0.003; P < .001), antidepressants (β = 0.046; SE = 0.013; P < .001), trazodone hydrochloride (β = 0.033; SE = 0.010; P < .001), anticonvulsants (β = 0.014; SE = 0.006; P = .03), and opioids (β = 0.038; SE = 0.007; P < .001) was observed. The absolute difference in observed vs estimated use in the last week of the pandemic period ranged from 0.48% (for anticonvulsants) to 1.52% (for antipsychotics). No significant level or slope changes were found for antibiotics, ARBs, or ACE inhibitors. In this population-based cohort study, statistically significant increases in the use of antipsychotics, benzodiazepines, antidepressants, anticonvulsants, and opioids followed the onset of the COVID-19 pandemic, although absolute differences were small. There were no significant changes for antibiotics, ARBs, or ACE inhibitors. Studies are needed to monitor whether changes in pharmacotherapy persist, regress, or accelerate during the course of the pandemic and how these changes affect resident-level outcomes.

New Pharmaceutical Salts of Trazodone.

New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.

Improvement of Advanced Assisted gastro retentive floating tablet using TRZ and S

Definition advancement is a significant piece of medication plan and improvement. Bioavailability and bioequivalence are absolutely reliant on definition improvement. Presently a-days detailing advancement is finished by following Quality through Design. Floating drug conveyance frameworks are the gastro retentive structures that absolutely control the delivery pace of target medication to a particular site which encourage a tremendous effect on medical care. This can be accomplished by utilization of different polymeric substances. Trazodone-Hydrochloride (TRZ), is a notable substance aggravate that is utilized as an energizer that has a place with a particular serotonin repeated inhibitors (SARI). The delivery information was fitted to different numerical models, for example, higuchi, Korsmeyer-Peppas (KP), 1st request &amp;0 request to assess the energy and system of the medication discharge. Arranged coasting tablets of TRZ may end up being a possible possibility for sheltered and successful controlled medication conveyance over an all-encompassing timeframe for gastro retentive medication conveyance framework. The oral assisted medication architecture conveyance has been confounded through confined habitation time gastric. Also, rapid gastro-intestinal transmission might predict overall discharge medication in zone of retention and diminish the handled portion adequacy, as many of medications have been invested on small digestive upper piece system. Also, it handles structure measurement at assimilation site &amp; in this way updates bio-availability as stated in.

Quantitative determination of Trazodoe hydrochloride in bulk and pharmaceutical dosage form by Zero order and AUC by UV-spectrophotometry

Two simple UV-Spectrophotometric methods have been developed for estimation of trazodone HCl (TZH) in bulk and pharmaceutical formulation form by using Zero order UV spectrometric absorbance method (method I) and Zero order UV spectrometric method using area under curve technique (method II). Water was used as solvent. In these Method ? max was found to be 246.0 nm of TZH and AUC between two wavelengths 235.20 nm – 256.60 nm. In both method Linearity in the concentration range of 05-35 mg/ml (r2>0.99)for TZH. Proposed methods were applied for oral dosage and amounts of TZH estimated by method I were found to be 99, by Method II were found to be 98.80 respectively. Both these methods were validated statistically and by recovery experiments. Keywords: Trazodone hydrochloride(TZH), UV spectrometric, Zero order, AUC.

Physiologically Based Dissolution Testing in a Drug Development Process\u2014a Case Study of a Successful Application in a Bioequivalence Study of Trazodone ER Formulations Under Fed Conditions

Development of generic extended-release (ER) formulations is challenging. Especially under fed conditions, the risk of failure in bioequivalence trials is high because of long gastric residence times and susceptibility to food effects. We describe the development of a generic trazodone ER formulation that was aided with a biorelevant dissolution evaluation. Trazodone hydrochloride 300-mg monolithic matrix tablets were dissolved both in USP and EMA compliant conditions and in the StressTest device that simulated both physicochemical and mechanical conditions of the gastrointestinal passage. The final formulation was tested against the originator, Trittico XR 300 mg, in a randomized cross-over bioequivalence trial with 44 healthy volunteers, in agreement with EMA guidelines. Initially developed formulations dissolved trazodone similarly to the originator under standard conditions (f2 factor above 50), but their dissolution kinetics differed significantly in the biorelevant tests. The formulation was optimized by the addition of low-viscosity hypromellose and mannitol. The final formulation was approved for the bioequivalence trial. Calculated Cmax were 1.92 ± 0.77 and 1.92 ± 0.63 [μg/mL], AUC0-t were 27.46 ± 8.39 and 29.96 ± 9.09 [μg∙h/mL], and AUC0-∞ were 28.22 ± 8.91 and 30.82 ± 9.41 [μg∙h/mL] for the originator and test formulations, respectively. The 90% confidence intervals of all primary pharmacokinetic parameters fell within the 80–125% range. In summary, biorelevant dissolution tests supported successful development of a generic trazodone ER formulation pharmaceutically equivalent with the originator under fed conditions. Employment of biorelevant dissolution tests may decrease the risk of failure in bioequivalence trials of ER formulations.

Trazodone as a mediator of transitional stress in a shelter: Effects on illness, length of stay, and outcome

Companion dogs housed in animal shelters are subject to a great number of uncontrollable and unalterable stressors. To combat these stressors and the associated immunosuppression that can result in high rates of contagious disease in sheltered dogs, a large open admission municipal animal shelter in New York City introduced trazodone hydrochloride, a serotonin receptor antagonist and reuptake inhibitor, to help reduce their transitional stress. Dogs were given low doses of trazodone at intake (5 mg/kg), one to two doses within 48 hours of arrival. Prevalence of illness was calculated for two time periods at the Brooklyn and Manhattan Care Center locations (N = 1,766): November and December 2018, when trazodone was administered to the population, and a historical control in November and December 2017 and 2016, when no trazodone was administered. A statistically significant difference in the percentage of sick dogs was found when comparing the No Trazodone group (2016/2017) and Trazodone treatment group in 2018 (Chi2 [1, N = 1766] = 19.4, P < 0.001). An increased percentage of sick dogs was observed in the No Trazodone group (41%) compared with the Trazodone treatment group (29%). Moreover, a significant difference in the average length of stay (LOS) in the shelter was observed when comparing the two groups (t (1764) = 2.71, P = 0.007). The average LOS was longer for the dogs in the No Trazodone group (M = 10.47, standard deviation [SD] = 8.53) than that for those in the Trazodone treatment group (M = 9.23, SD = 6.57). Finally, a significant difference was observed in the percent of adoptions between the two groups (Chi2 [1, N = 1766] = 19.4, P < 0.001). A larger percentage of dogs were adopted in the Trazodone treatment group (42%) than in the No Trazodone group (30%). While correlational, the preliminary results of this study suggest that trazodone may be effective in reducing illness and increasing adoptions by decreasing transitional stress in dogs living in a shelter setting.

Trazodone Loaded Lipid Core Poly (\u03b5-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation

Trazodone hydrochloride (TRH) is a lipophilic drug which is used effectively as an antidepressant. Its poor solubility and short half-life represent an obstacle for its successful use. Nanocapsules with biodegradable polymeric shell are successful drug delivery systems for controlling the release of drugs. To enhance the entrapment of lipophilic drugs, oils can be added forming a lipophilic core in which the drug is more soluble. The aim of this study was to enhance the efficacy of TRH and prolong its action by formulating it into lipid core polymeric shell nanocapsules. Nanocapules were prepared using nanoprecipitation technique. All prepared formulations were in nano size range and negatively charged. The TRH entrapment efficiency (EE%) in lipid core nanocapsules was up to 74.8 ± 0.5% when using Labrafac lipophile as a lipid core compared to only 55.7 ± 0.9% in lipid free polymeric nanospheres. Controlled TRH release was achieved for all prepared formulations. Forced swim test results indicated the significant enhancement of antidepressant effect of the selected TRH loaded Labrafac lipophile core nanocapsules formulation compared to control and TRH dispersion in phosphate buffer. It is concluded that lipid core nanocapsules is a promising carrier for the enhancement of TRH efficacy.

FORMULATION DEVELOPMENT AND EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF TRAZODONE HYDROCHLORIDE

FORMULATION DEVELOPMENT AND EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF TRAZODONE HYDROCHLORIDE Vivek Jain1, Halki Kushwah*1, Anwar Iqbal Khan1, Geeta Parkhe2 NRI Institute of Pharmacy, Bhopal, Madhya Pradesh, India. ABSTRACT Formulation development is an important part of drug design and development. Bioavailability and bioequivalence are totally dependent on formulation development. Now-a-days formulation development is done by following QbD (Quality by Design).Floating drug delivery systems are the gastro retentive forms that precisely control the release rate of target drug to a specific site which facilitate an enormous impact on health care. This can be achieved by use of various polymeric substances. Trazodone Hydrochloride (TRZ), is a well-known chemical compound that is used as an antidepressant that belongs to a selective serotonin reuptake inhibitors (SARI). TRZ is used as anti-anxiety and sleep-inducing agent. The tablets of TRZ were prepared by direct compression method using gas generating agent and different polymer combinations. The prepared tablets of TRZ were evaluated for hardness, thickness, friability, weight variation, drug content uniformity, buoyancy lag time, total floating time, swelling index, in-vitro dissolution study, etc. All the compositions were resulted in adequate Pharmacopoeial limits. The varying concentration of gas generating agent and polymers was found to effect on in-vitro drug release and floating lag time. In vitro drug release of floating gastro retentive tablet of TRZ shown that the formulation F9 was found to be the best formulation as it releases 97.98% TRZ in a controlled manner for an extended period of time (up to 12 hours). The release data was fitted to various mathematical models such as higuchi, Korsmeyer-Peppas, first order and zero order to evaluate the kinetics and mechanism of the drug release. Prepared floating tablets of TRZ may prove to be a potential candidate for safe and effective controlled drug delivery over an extended period of time for gastro retentive drug delivery system. Keywords: Trazodone Hydrochloride, Gastro retentive, floating tablet, Total floating time. Full Text Article