AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2637-8892/045
Department of Psychological Medicine, Rheinfelden, Switzerland.
*Corresponding Author: Samuel Langhorne, Department of Psychological Medicine, Rheinfelden, Switzerland.
Citation: Samuel Langhorne, Eric Arthur Blair. (2017) Theoretical Uses of Pramipexole hydrochloride in Parkinson's Resistance Depression. J Psychology and Mental Health. 1(2); DOI: 10.31579/2637-8892/045
Copyright: © Samuel Langhorne. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 05 June 2018 | Accepted: 13 June 2017 | Published: 24 June 2017
Keywords: Keywords
Pramipexole dihydrochloride monohydrate is an antiparkinson’s agent which is known as dopamine D2 receptor agonist. It is structurally different from the ergot-derived drugs, e.g. bromocriptine or pergolide. Pramipexole is designated chemically as (S)-2-Amino-4, 5, 6, and 7-tetrahydro-6-(propylamino) benzothiazole and has the molecular formula C10H17N3S. It comes under class I of Biopharmaceutical Classification System. The purpose of this study was to develop and evaluate pramipexole dihydrochloride monohydrate extended release tablets by wet granulation method using different proportions of polymers and binder. Pre-formulation studies were done initially and the results were found to be within the limits. All the mentioned batches were prepared and granules were evaluated for pre-compression parameters such as loss on drying, bulk density, tapped density and compressibility index. Tablets were evaluated for weight variation, thickness, hardness, friability; disintegration time and assay were found to be within the limits. In vitro dissolutions were performed with 0.05M 6.8 PH phosphate buffer and effect of various polymers were explored. Final selection of formulation was based on dissolution profile, from dissolution studies formulation 9 showed 80% drug release within 20 hours, so it will be compared with innovator. Similarity and difference factors which revealed that formulation (F 9) containing HPMC K 200, Eudragit L100 and binder are most successful as it exhibited in vitro drug release that matched with innovator product. In vitro drug release profile reveals that with increased concentration of Eudragit L 100. Accelerated stability studies were performed for the optimized batch which indicated that there were no changes in drug content and in vitro dissolution.
Extended release drug delivery system
The main objective of any drug delivery system is to provide a correct dose of drug at the proper site in the body to achieve results, and then to maintain the desired drug concentration. Since there is increase in cost and compliance involved in the development and marketing of new drug entities, this has forced most of the pharmaceutical industries to focus their attention on the development of extended / controlled / prolonged system.
The extended release dosage forms are becoming popular as these have a number of advantages over conventional dosage from on dose frequencies, less fluctuation in circulating blood levels, increased patient compliance, and more uniform effect.
Extended release system consists of two parts.
1) An immediately available dose to establish the blood level concentration quickly.
2) An extended release portion or maintenance dose, which contains several times the therapeutic dose for maintaining the achieved blood level concentration. The main concept of controlled / extended drug delivery system is the use of the system and techniques for altering and controlling the absorption, blood levels metabolism, organ distribution and cellular uptake of pharmacologically active agents.
The main aim of the extended or controlled dosage form is to produce an improved therapy by producing a uniform plasma concentration of drug at steady state and by reducing the ratio of maximum and minimum plasma levels. [C max / C min] after each dose. This could be achieved if the release of drug from the dosage form is slow first order or slow zero order absorption of the drug occurs from the gastro intestinal tract.
The term “extended release” is known to have existed in the medical and pharmaceutical literature for many decades. It has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed and / or prolonged and its plasma profile is extended in duration. The onset of its pharmacological action is often delayed, and duration of its therapeutic effect is extended.
Figure-1: Hypothetical drug concentration profiles in the systemic circulation resulting from the consecutive administration of multiple dose of an immediate release drug delivery system (A1, A2)
Figure-2: Drug blood levels Versus Time Profiles showing the Relationship between Controlled Release (A), Prolonged Release (B) and Conventional Release (C) Drug Delivery.
List of chemicals used with their grades and supplier names
SI. No |
Materials |
Source |
1 | Pramipexole diHcl monohydrate |
A gift sample from Eros Pharma, Bangalore CFL Pharma, Goa
|
2 | Lactose monohydrate | Kelco Pharma |
3 | Microcrystalline cellulose PH 101 | Rohm Pharma. Bombay |
4 | Eudragit L 100 | Rohm Pharma. Bombay |
5 | HPMC E 3LV | SD Fine Chem., Bombay |
6 | Povidone K 90 | SD Fine Chem., Bombay |
7 | HPMC K4M | SD Fine Chem., Bombay |
8 | HPMC K 200 | SD Fine Chem., Bombay |
9 | MCC 112 | SD Fine Chem., Bombay |
10 | Aerosil 200 | SD Fine Chem., Bombay |
11 | Stearic acid | SD Fine Chem., Bombay |
Preformulation Studies
Drug-Excipients compatibility studies:
Method
Selected excipients were checked for any changes when thoroughly mixed with drug in fixed proportions and checked at various temperatures like 25°C/ 60% RH and 30°C/65% RH and 40°C/75% RH and it was observed that there were no changes in the physical properties namely appearance, colour etc.
Drug uses
All 11 patients with PD and pathological gambling were taking therapeutic doses of a dopamine agonist; 3 of these patients were not treated with levodopa. In 7 patients, pathological gambling developed within 3 months of starting to take or escalating the dose of the agonist; in the other 4 with a longer latency, gambling resolved after the agonist use was discontinued. Pramipexole dihydrochloride was the agonist in 9 of 11 cases in our series and 10 of 17 in the literature (68% in total).
Parkinson disease (PD) is primarily treated by drugs that restore or improve brain dopaminergic neurotransmission. Brain dopamine also plays a central role in the behavioral reward system of both humans and animals, reinforcing a myriad of both productive and counterproductive behaviors. It has been implicated in mediating the reward of gambling behavior.
Several recent reports have linked PD dopamine replacement therapy to pathological gambling. Within the last 3 years, 2 of us encountered 11 patients with PD and pathological gambling in our routine neurology practice (movement disorders). The gambling addiction had recently developed and was temporally related to use of dopamine agonist drugs.
Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in “on” periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs.
The present study was carried out to formulate and characterize oral extended release tablets of Pramipexole dihydrochloride monohydrate by wet granulation method. The tablets were prepared by using different combination of polymers viz. HPMC K4M, HPMC 3LV, and Eudragit L- 100.
Treatment population
Profile of the randomised trial: flow diagram with the progress of the patients throughout the trial.
The results are summarized as follows. Similarly FT-IR spectra of Prampexole dihydrochloride monohydrate in combination with polymers are shown in Figures 4 to 8. These peaks were not affected and prominently observed in FT-IR spectra given in Figures 4 to 8. This indicates that there is no interaction between Prampexole dihydrochloride monohydrate and polymers and the drug was compatible with the formulation components.
FTIR graph of pure drug of Prampexole dihydrochloride monohydrate
Results of Drug and excipients compatibility study.
S.No. | Drug and excipients | Ratio | Observation |
1 | API and lactose monohydrate | 1:5 | NCC |
2 | API and MCC | 1:5 | NCC |
3 | API and Eudragit | 1:5 | NCC |
4 | API and HPMC 3LV | 1:5 | NCC |
5 | API and HPMC K4M | 1:5 | NCC |
MirapexER fitted in Higuchi model.
The conclusions drawn from the present investigation were given below:
Suitable analytical method based on UV-Visible spectrophotometer was developed for Pramipexole dihydrochloride monohydrate lmax of 260 nm was identified in pH 6.8 Phosphate buffer.
From the FT-IR spectra the interference was verified and found that pramipexole dihydrochloride did not interfere with the excipients used. Procedure to manufacture extended tablets by Wet granulation method was established.
The tablets were evaluated for pharmacopoeial and non-pharmacopoeial (industry specified) tests. Based on the results, F-IX was identified as better formulation amongst all formulations developed for matrix tablets.
Tablets of the formulation F-IX passed all official and unofficial quality control tests.
In vitro release profiles of optimized formulations of pramipexole dihydrochloride monohydrate tablets (F-IX) were found to be similar to that of theoretical drug release profile. The f1 and f2 values for the comparison of release of drugs from the formulation F-IX with the theoretical drug release profile were found to be 7, 67 in 6.8 Phosphate buffer.
Pramipexole dihydrochloride monohydrate release from the tablets of F-IX formulation follows zero- order kinetics.
Pramipexole dihydrochloride monohydrate release from the tablets of F-IX formulation follows Higuchi model. Release mechanism of pramipexole dihydrochloride monohydrate from tablets of F-IX formulation follows Diffusion- rate limited mechanism. According Krosmeyer-Peppas the mechanism was Anomalous (Non-Fickian) diffusion.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
