Trihexyphenidyl HCl Research Articles

A STUDY OF OFF LABEL DRUG USE IN PSYCHIATRY DEPARTMENT AT TERTIARY CARE HOSPITAL

Background: US-Food and Drug Administration has dened off-label drug as “use of drugs for the indication, dosage form, regimen, patient or other use constraint not mentioned in the approved labeling.” Off-label prescription is common in Psychiatry. The aim of this study is to evaluate such off-label drug use in psychiatry department of a tertiary care teaching hospital. An observational, cross sectional study was Methods: conducted among 150 patients attending Psychiatry outpatient department for the period of 3 months. Data related to demographic parameters, diagnosis and prescription details were collected directly from the patient's medical records and entered in Case Record Form (CRF).The off-label drugs were categorized as per National Formulary of India and CDSCO list of approved drug use. Total 150 patients were included in this Results: study with mean age of 43.6 years. Most of the patients were diagnosed with Schizophrenia [N=36, 24%]. Out of 150, 90 patients [60%] received at least 1 off label drug. Total 478 drugs were prescribed, out of which 144 [30.12%] were off label according to CDSCO and 145 [30.33%] were off label according to NFI. The drugs most frequently prescribed as off label drug according to CDSCO were Vitamins & Minerals [13.59%], Clonazepam [2.92%], Trihexyphenidyl HCL [2.09%], Diazepam [1.88%]. The drugs most frequently prescribed as off label according to NFI were Vitamins & Minerals [12.76%], Aripiprazole [2.09%], and Trihexyphenidyl HCL [2.09%]. Off label drug Conclusion: s used among psychiatry patients was 30.12%. The most frequently used off-label drugs were Vitamins & Minerals followed by Clonazepam & Trihexyphenidyl HCL. The use of off-label drugs in psychiatric patients has been reportedly increasing which warrant national drug regulatory authorities to review and revise safe administration such drugs.

Pattern and treatment of Parkinson’s disease at different health care levels in Bangladesh: a hospital based survey

<p class="abstract"><strong>Background:</strong> Parkinson’s disease (PD) is a condition in which part of the brain becomes progressively damaged over many years. This study represents the pattern of Parkinson’s disease and help to identify various drugs which are being used at different health care levels in Bangladesh.</p><p class="abstract"><strong>Methods:</strong> Cross-sectional technique was applied as study design in this research work. We accessed the patients with formulated questionnaire of the Department of Neuroscience of National Institute of Neurosciences and Hospital, Dhaka Medical College and Hospital and Bangabandhu Sheikh Mujib Medical University (BSMMU) for data collection from January 2017 to August 2019. 100 patients were selected in the ages between 25-80 years, among them 66 were male and 34 females. </p><p class="abstract"><strong>Results:</strong> A total number of 100 Parkinson’s disease patients (male 66%, female 34%) were recruited for this study. Genetic factor (56%) is the main cause of PD found in this study. Among various symptoms, the prominent symptoms were voice disorders (96%), slowness of movement (90%), mask-like face expression (86%), tremor (80%), sensory and sleep difficulties (78%), excessive sweating (60%) and insomnia (56%). It was observed that along with physiotherapy, drugs used to manage PD were levodopa (14%), carbamazepine (12%), quetiapine (12%), haloperidol (11%), pramipexole (10%), trihexyphenidyl HCl (10%), carbidopa (8%), amlodipine (8%) and clonazepam (8%).</p><p class="abstract"><strong>Conclusions:</strong> Disgrace exists in the personal life and social context of the PD patients which also unfavourably affects their psychosocial aspects of life. Our population-based data provide evidence for a protective effect of Parkinson’s disease in our country.</p>

Off-label drug use in Psychiatry Outpatient Department: A prospective study at a Tertiary Care Teaching Hospital.

Introduction:Off-label drug prescribing is very common in Psychiatry. US-Food and Drug Administration has defined off-label drug as “use of drugs for the indication, dosage form, regimen, patient or other use constraint not mentioned in the approved labeling.”Objective:The objective was to evaluate off-label drug use in patients attending Outpatient Department of Psychiatry.Materials and Methods:One year prospective, cross sectional study was conducted on patients attending Psychiatry Outpatient Department. Demographic data, clinical history, and complete prescription were noted in the predesigned proforma and prescriptions were analyzed for off-label drug use as per British National Formulary-2011.Result:A total of 250 patients were enrolled with mean age 40.36 ± 12.3 years. Most common diagnosis was major depressive disorder 101 (40.4%). A total of 980 drugs (mean 3.68 ± 1.42) were prescribed out of which 387 (39.5%) were off-label. Of 250 patients, 198 (79.2%) received at least one off-label drug. Psychopharmacological agents most frequently used in off-label manner were clonazepam 31 (12.4%), lorazepam 30 (12%), and trihexyphenidyl HCl 25 (10%). Prevalence of off-label use of these three drugs was significantly higher than other off-label drugs (P < 0.0001, P < 0.0001 and P < 0.0001 respectively). Inappropriate indication was the most common category of off-label use. There was positive and significant correlation between off-label prescribing and number of drugs (r = 0.722, P ≤ 0.000). Off-label prescribing was statistically significantly higher in 21–40 year age group, but no difference was seen in any co-morbid condition or in between any psychiatric disorder.Conclusion:Off-label drugs use is common in psychiatric OPD in our setup. Clonazepam, lorazepam, and trihexyphenidyl HCl were the most frequently used drugs in off-label manner.

Formulation and evaluation of bi-layer floating tablets of ziprasidone HCl and trihexyphenidyl HCl

The purpose of this research study was to establish ziprasidone HCl NR 40 mg and trihexyphenidyl HCl SR 4mg in the form of bi-layer sustained release floating tablets. The tablets were prepared using sodium HPMC K4M / HPMC K15M as bio-adhesive polymers and sodium bicarbonate acting as a floating layer. Tablets were evaluated based on different parameters such as thickness, hardness, friability, weight variation, in vitro dissolution studies, content of active ingredient and IR studies. The physico-chemical properties of the finished product complied with the specifications. In vitro release from the formulation was studied as per the USP XXIII dissolution procedure. The formulations gave a normal release effect followed by sustained release for 12 h which indicates bimodal release of ziprasidone HCl from the matrix tablets. The data obtained was fitted to Peppas models. Analysis of n values of the Korsmeyer equation indicated that the drug release involved non-diffusional mechanisms. By the present study, it can be concluded that bi-layer tablets of ziprasidone HCl and trihexyphenidyl HCl will be a useful strategy for extending the metabolism and improving the bioavailability of Ziprasidone HCl and Trihexyphenidyl HCl.

Formulation and Evaluation of Extended Release Trihexyphenidyl Hydrochloride Hard Gelatin Capsules

This work aims at investigating different types and levels of hydrophilic high molecular weight matrix agents, (including HPMC K15M, Metalose-60 SH, Metalose-65 SH and Metalose-90SH-SR), hydrophobic diluent (Talc) and formulation methods (Non-aqueous granulation and direct filling by simple mere mixture) in an attempt to formulate hard gelatin extended release matrix capsules containing Trihexyphenidyl HCl (Benzhexol). The drug release from all the extended release matrix capsules show polymer as well as talc concentration dependent retardation affect. The Metalose 90SH-SR concentration was optimized to approximately 27% w/w of total capsule net content weight. The hydrophobic diluent’s talc concentration was optimized and the useful concentration was approximately 17.45% w/w of the total net capsule content weight. The lactose concentration was also optimized and the effective concentration was found to be approximately 48.36% w/w. The prepared hard gelatin extended release capsules were evaluated for weight variation, Average net content, locked length, content uniformity, assay (drug content) and in-vitro drug release studies. From the in-vitro release studies of the prepared formulations, one formula was optimized from each method. All the formulations showed linear release profiles and extended the release of trihexyphenidyl HCl (Benzhexol) over 10 –12 h. The release profiles of extended release matrix capsules of trihexyphenidyl HCl (THP HCl) from the selected formulations were close to zero order and follow diffusion dependent release. The prepared extended release matrix capsules of trihexyphenidyl HCl (Benzhexol) produced from the optimized formulations ‘NAG-M90SH-SR-5 and DB M90SH-SR-4’ complied with the USP XXVII specifications. The difference factor (f1) and similarity factor (f2) was calculated for all these formulations and found to the below 15 and above 50. Irrespective of the formulation method type and its procedure, the prepared hydrophilic extended release matrix capsules showed non-Fickian anomalous transport (coupled diffusion in the hydrated matrix and polymer relaxation) as the values of release exponent (n) are in between 0.50 and 0.89. Finally it was clear that it is possible to design a formulation with any of the above two methods giving the desired drug release profile suggesting that nonaqueous granulation, Direct filling were good methods for preparing extended release matrix capsules of trihexyphenidyl HCl (Benzhexol).

Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes

The purpose of this work was to characterize a novel ethosomal carrier containing trihexyphenidyl HCl (THP) and to investigate the delivery of THP from ethosomes versus classic liposomes. THP-ethosomal systems were shown by electron microscopy to contain small, phospholipid vesicles. As the THP concentration was increased from 0 to 3%, the size of the vesicles decreased from 154 to 90 nm. This is most likely due to the surface activity of THP (critical micelle concentration of 5.9 mg/ml), as measured in this work. In addition, the ethosome zeta potential value increased as a function of THP concentration, from −4.5 to +10.4 when the THP concentration was increased from 0 to 3%. In contrast, THP liposomes were much larger and their charge was not affected by THP. When compared with standard liposomes, ethosomes had a higher entrapment capacity and a greater ability to deliver entrapped fluorescent probe to the deeper layers of skin. The flux of THP through nude mouse skin from THP ethosomes (0.21 mg/cm 2 h) was 87, 51 and 4.5 times higher than from liposomes, phosphate buffer and hydroethanolic solution, respectively ( p<0.01). The quantity of THP remaining in the skin at the end of the 18-h experiment was statistically significantly greater from the ethosomal system than from liposomes or a control hydroethanolic solution. Our results indicate that the ethosomal THP system may be a promising candidate for transdermal delivery of THP.

Muscarinic M 1, M 2 receptor binding. Relationship with functional efficacy

A comparison has been made between [ 3H]pirenzepine binding to the M 1 receptor population of rat cerebral cortex and [ 3H]N-methylscopolamine binding to M 2 receptors in rat cardiac membranes. Several standard muscarinic antagonists including trihexyphenidyl HCl, benztropine, biperidin and 4-DAMP (4-diphenylacetoxy-N-methyl piperidine methiodide) showed some selectivity for the M 1 binding assay. Dicyclomine and hexahydrosiladifenidol were the only antagonists with a selectivity approaching that of pirenzepine. Gallamine and AFDX-116 were the only M 2 (cardiac) selective antagonists. Muscarinic agonists displayed profiles which could be classified into two groups, apparently related to their intrinsic activity. One group displayed apparent selectivity for the heart, with low Hill coefficients and contained full agonists such as acetylcholine. The second group displayed less selectivity, intermediate Hill coefficients and contained partial agonists such as pilocarpine. Thus muscarinic agents can distinguish between different tissues not only on the basis of receptor selectivity, but also by recognition of high and low agonist affinity states. Thus the intrinsic activity of a muscarinic agonist may reflect an apparent but not true receptor-mediated selectivity.

Pharmacokinetic Evaluation of a Sustained-release Formulation of Trihexyphenidyl in Healthy Volunteers

Twenty-four male subjects were randomized to receive two oral dosage forms of trihexyphenidyl HCL (α-cyclohexyl-α-phenyl-1-piperidinepropanol HCL). The dosage regimens were (1) a 5-mg immediate release (IR) tablet given twice daily at time zero and 12h later, and (2) two 5-mg sustained-release (SR) capsule formulations given daily. The number of adverse experiences following the SR formulation were ~50% of those for the IR formulation, the peak concentration (Cmax) after the SR formulation was significantly lower (p < 0.05) than that after the first dose of the IR formulation, and the time to reach Cmax(tmax) was significantly longer after the SR formulation (p < 0.05). The SR formulation maintained serum concentrations above 50, 60, and 70% of Cmax values for average time periods of 11.7, 9.4, and 5.9 h, respectively, compared with values of 1.8, 1.2, and 0.9h after the IR formulation; the differences were all significant (p < 0.05). The mean elimination half-life (t1/2) was similar (p > 0.05) after the SR (10.1 h) and IR (8.7 h) formulations. The statistical power of the study was 98.1% to detect a 20% difference in the area under the curve from time zero to time infinity (AUC0→∞) between formulations. Although the AUC0→∞ after the SR formulation was statistically smaller (p < 0.05) than after the IR tablet, the difference was <20%. Therefore, the SR formulation was bioequivalent to the IR tablet formulation of trihexyphenidyl.

Effect of anti-parkinsonism drugs on gastric emptying and intestinal transit in the rat.

The effect of atropine sulfate, trihexyphenidyl HCl, benztropine mesylate, diphenhydramine HCl and ethopropazine HCl on gastric emptying and intestinal transit of a phenol red solution in the rat was examined. Intraperitoneal administration of 0.3 mg/kg atropine, 1.2 mg/kg benztropine and trihexyphenidyl results in a marked decrease in gastric emptying and intestinal transit rate when compared to controls. Oral administration of these agents produced variable and unpredictable results. Single and multiple oral dose (0.6--3 mg/kg) studies with trihexyphenidyl failed to produce any significant decreases in gastric emptying rates. A single oral dose of benztropine (0.6--3 mg/kg) failed to reduce the gastric emptying rate, but multiple dose studies produced a significant decrease in the gastric emptying rate. Effects on gastric emptying and intestinal transit were seen after single and multiple oral doses of diphenhydramine and ethopropazine.

Central nervous system and autonomic nervous system effects of amantadine and of some standard anti-Parkinson drugs.

The activity of amantadine HCl, trihexyphenidyl HCl, ethopropazine HCl, atropine sulphate, mecamylamine HCl and L-dopa against effects provoked by nicotine injected intracerebrally(tremors, convulsions, loss of righting reflex) was studied. The antagonistic drugs were injected intraperitoneally or intracerebrally.The above mentioned drugs except L-dopa and atropine preventednicotine manifestations when given intraperitoneally. Amantadine, atropine and mecamylamine, resulted active when given intracerebrally (trihexyphenidyl, ethopropazine and L-dopa could not betested i.e.). Effects provoked by oxotremorine were counteracteby atropine, trihexyphenidyl, ethopropazine but not by amantadineand mecamylamine. Trihexyphenidyl, ethopropazine and atropine had anticarbamylcholine activity and mydriatic activity. Amantadine and mecamylamine were inactive or almost inactive.