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Drug Delivery and Translational Research Oct 2019The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of...
The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of dimenhydrinate. Final composition of SEDDS was established based on drug solubility and stability studies. Dimenhydrinate was loaded into the SEDDS pre-concentrates to 7.5% (m/v). The droplet size of the final SEDDS formulations was in a range between 60 and 220 nm. Permeability, as well as tissue toxicity, of the formulations was investigated using bovine nasal mucosa. Enhancement in permeation up to 2.8-fold compared to pure dimenhydrinate was confirmed. Furthermore, toxicity studies did not reveal any serious tissue damages related to the SEDDS. Additionally, irritation potential of SEDDS was evaluated in ciliary beat frequency measurements. Incorporation of dimenhydrinate into SEDDS might therefore be considered as a promising approach within the field of nasal delivery of antiemetics by utilizing permeation enhancement strategy.
Topics: Administration, Intranasal; Animals; Antiemetics; Cattle; Cilia; Dimenhydrinate; Drug Delivery Systems; Drug Liberation; Emulsions; In Vitro Techniques; Nasal Mucosa; Permeability; Solubility
PubMed: 30877627
DOI: 10.1007/s13346-019-00634-1 -
Advanced Pharmaceutical Bulletin Nov 2018To develop fast dissolving oral film to address vomiting and nausea in pediatric population. Oral films of Dimenhydrinate were prepared by solvent casting method by...
To develop fast dissolving oral film to address vomiting and nausea in pediatric population. Oral films of Dimenhydrinate were prepared by solvent casting method by using hydroxypropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 400 (PEG 400) and croscarmellose sodium. Solubility of dimenhydrinate was enhanced by ethanol as a co-solvent. To make dimenhydrinate palatable sodium saccharin and peppermint oil were used. All films were evaluated for mechanical parameters, surface pH, morphology, disintegration time and percent dissolution. Films were smooth, acceptable and white in colour. For optimized batch, drug content (99.106%), disintegration time (25 sec), dissolution (99.10% in 210 sec), surface pH (6.81) were acceptable. Optimized batch, due to its potential to deliver through fast dissolving film, can be developed for clinical use.
PubMed: 30607345
DOI: 10.15171/apb.2018.081 -
Biomedicine & Pharmacotherapy =... Jan 2019Colorectal cancer (CRC) is the most common carcinoma of the digestive tract. The slow growing nature of CRC offers a great opportunity for prevention strategies. The...
Colorectal cancer (CRC) is the most common carcinoma of the digestive tract. The slow growing nature of CRC offers a great opportunity for prevention strategies. The concept of chemoprevention of colorectal cancer using plant derived natural products is gaining substantial attention because it is an inherently safe and cost-effective alternative to conventional cancer therapies. Piperlongumine (PL), a natural alkaloid present in Piper longum Linn has been reported to exhibit notable anticancer effects in various in vitro studies. Nonetheless, the chemopreventive potential of PL has not been studied in experimentally induced colon cancer yet. Ras/PI3K/Akt/mTOR signaling axis plays a central role in promoting tumor cell growth, proliferation and survival by inhibiting apoptosis. In the present study, we demonstrated, for the first time, the chemopreventive effects of PL in DMH + DSS induced colon carcinogenesis animal model. We showed that PL displayed potent antineoplastic activity against colon cancer cell growth by targeting Ras proteins and PI3K/Akt signaling cascade. PL mediated inhibition of tumor cell growth was associated with inhibition of Ras protein levels and its preferred companion protein PI3K levels that led to suppressed activity of Akt/NF-κB, c-Myc and cyclin D1. It was also found that PL arrested the cell cycle progression at G2/M phase and induced mitochondrial apoptotic pathway by downregulating Bcl-2 levels. Furthermore, the results of liver and kidney toxicity suggested that PL exhibit no toxicity in animals. Our results suggest that PL may be an effective chemopreventive agent for colon cancer.
Topics: Alkaloids; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Dextran Sulfate; Dimenhydrinate; Dioxolanes; G2 Phase Cell Cycle Checkpoints; Male; Mice; Mice, Inbred BALB C; Phosphatidylinositol 3-Kinases; Piper; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 30551398
DOI: 10.1016/j.biopha.2018.10.182 -
Deutsches Arzteblatt International Oct 2018Seasickness and travel sickness are classic types of motion illness. Modern simulation systems and virtual reality representations can also induce comparable symptoms.... (Review)
Review
BACKGROUND
Seasickness and travel sickness are classic types of motion illness. Modern simulation systems and virtual reality representations can also induce comparable symptoms. Such manifestations can be alleviated or prevented by various measures.
METHODS
This review is based on pertinent publications retrieved by a PubMed search, with special attention to clinical trials and review articles.
RESULTS
Individuals vary in their susceptibility to autonomic symptoms, ranging from fatigue to massive vomiting, induced by passive movement at relatively low frequencies (0.2 to 0.4 Hz) in situations without any visual reference to the horizontal plane. Younger persons and women are considered more susceptible, and twin studies have revealed a genetic component as well. The various types of motion sickness are adequately explained by the intersensory conflict model, incorporating the vestibular, visual, and proprioceptive systems and extended to include consideration of postural instability and asymmetry of the otolith organs. Scopolamine and H1-antihistamines, such as dimenhydrinate and cinnarizine, can be used as pharmacotherapy. The symptoms can also be alleviated by habituation through long exposure or by the diminution of vestibular stimuli.
CONCLUSION
The various types of motion sickness can be treated with general measures to lessen the intersensory conflict, behavioral changes, and drugs.
Topics: Fatigue; Histamine Antagonists; Humans; Motion Sickness; Neurophysiology; Vomiting
PubMed: 30406755
DOI: 10.3238/arztebl.2018.0687 -
Frontiers in Pharmacology 2018The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from... (Review)
Review
The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) -originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) -searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) -investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) metoclopramide was initially assumed to act only via D receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT receptors. The latter led to identification of selective 5-HT receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) -antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years.
PubMed: 30233361
DOI: 10.3389/fphar.2018.00913 -
Galen Medical Journal 2018Design, formulation and physicochemical evaluation of dimenhydrinate 25 mg oral tablets that disintegrate in oral cavity in a proper time. This product is easy to use...
BACKGROUND
Design, formulation and physicochemical evaluation of dimenhydrinate 25 mg oral tablets that disintegrate in oral cavity in a proper time. This product is easy to use for babies, geriatrics and people who have difficulty in swallowing.
MATERIALS AND METHODS
31 formulations were designed in 3 categories via Design-Expert software version 7. Group 1 consist of super-disintegrating bases, group 2 consist of effervescent bases and group 3 consist of super-disintegrating and effervescent bases together. Proposed by DesignExpert software, the optimum formulations were selected in each category and the tablets were produced by direct compression method. Tablets evaluated by friability, thickness, hardness, weight variation, drug content, content uniformity, disintegration time, wetting time, dissolution and moisture uptake tests.
RESULTS
The angle of repose and compressibility index of formulations were in the range of 24.65-29.08 and 5.02-9.01 % respectively. Thickness, hardness, wetting time, friability and content uniformity of formulations were in the range of 3.36-3.84 mm, 33.25-38.03 N, 19-37 seconds, 0.31-0.42 % and 96.44-99.02 % respectively. Disintegration time of the groups 1, 2 and 3 were in the range of 16-70, 47-72 and 12-35 seconds respectively.
CONCLUSION
Mixture of powders and orally dispersible tablets passed all tests. The results showed that formulations containing both of super-disintegrants and effervescent bases had better disintegration time compare to other formulations.
PubMed: 34466419
DOI: 10.22086/gmj.v0i0.936 -
Indian Journal of Otolaryngology and... Dec 2017Migraine related vertigo (MRV) is largely accepted in the vestibular community and probably represents the second most common cause of vertigo after benign positional...
Migraine related vertigo (MRV) is largely accepted in the vestibular community and probably represents the second most common cause of vertigo after benign positional vertigo by far exceeding Meniere's disease. The data on vestibular migraine management is still relatively poor, despite its enormous importance in daily practice. A 55-year old male presented with history of giddiness, imbalance, sweating and sensation of nausea with severe pulsating headache of one day duration. Ear, Nose and Throat examination was normal. Neurological tests were negative. Audiogram and Electronystagmography were within normal limits. Nystagmus was positive on turning his head to left side. By reviewing the available literature on MRV, the report aims to outline a protocol for future management. The patient and caretakers were thoroughly counseled and educated, started on Flunarizine 10 mg and Dimenhydrinate 50 mg; advice healthy life style, necessary precautions, compliance to treatment. Patient was reportedly followed up and was symptom free over a period of 9 years. There is a call for proper diagnosis to address the complaint and manage of symptoms in acute attack and prophylaxis. In addition, this case highlight the ongoing need for proper systematic evaluation, therapeutic management, follow up by ensuring compliance to medication, necessary precautions and life style modification.
PubMed: 29238692
DOI: 10.1007/s12070-017-1101-x -
Scientific Reports Aug 2017The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel...
Intranasally administered in situ gelling nanocomposite system of dimenhydrinate: preparation, characterization and pharmacodynamic applicability in chemotherapy induced emesis model.
The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel network composed of poloxamer and hyaluronic acid for the intranasal delivery of the antiemetic dimenhydrinate (DMH). PEVs were prepared using phospholipids and labrasol/transcutol/PEG 400 as penetration enhancers, and characterized for entrapment efficiency (EE%), particle size, zeta potential and morphology. The nanocomposite in situ forming gel system was characterized for its sol-gel temperature, viscosity and mucoadhesiveness, and was pharmacodynamically tested on a cisplatin induced emesis model in rats in terms of food, water, kaolin intake and stomach weight content. The selected PEVs formula displayed EE% of 83% for DMH, particle size of 121 nm and a surface charge of 0.83 mV. The selected nanocomposite in situ gelling formula showed a viscosity of 2.13 Pa.S, mucoadhesive force of 0.62 N and DMH controlled release over 6 hours. The pharmacodynamic study showed the superiority of the nanocomposite in situ gelling formula; being administered at a lower dose than the oral marketed formula. The described nanocomposite system proved to be successful for the intranasal delivery of DMH, thus presenting a promising delivery modality for similar antiemetics.
Topics: Administration, Intranasal; Animals; Antiemetics; Cisplatin; Dimenhydrinate; Drinking; Drug Compounding; Eating; Gels; Male; Microscopy, Electron, Transmission; Molecular Structure; Nanocomposites; Rats, Wistar; Viscosity; Vomiting
PubMed: 28855590
DOI: 10.1038/s41598-017-10032-7 -
Medycyna Pracy May 2017The phenomenon of stupefying by the use of available over-the-counter drugs (OTC) among adolescents is an essential problem in both Poland and throughout the world.... (Review)
Review
The phenomenon of stupefying by the use of available over-the-counter drugs (OTC) among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM), pseudoephedrine/ephedrine, codeine (methylmorphine), dimenhydrinate, paracetamol (acetaminophren) and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported. The test results cited by the authors clearly indicate that the use of OTC drugs, whose turnover is not controlled is a domain of females. The extent of use of drugs not prescribed by a doctor has remained for many years at a constant level. The most common poisonings with OTC drugs are caused by those that affect the respiratory system or exert analgesic or antipyretic effects. They are also used in attempted suicides, especially among females. Analyzing poisonings caused by OTC medications their seasonality has been observed. Their number increases during spring-autumn. A territorial differentiation in areas of OTC drug trade in terms of their quantities, with the predominance of southern regions is also noted. Intoxication with psychoactive substances causes the deterioration of relations between young people. In the reviewed studies there is no detailed information on the composition of non-prescription medicines. Moreover, young people have easy access to mushroom fungi, growing in nearby forests and meadows that may have hallucinogenic effects and are available in pharmacies and on the Internet. Med Pr 2017;68(3):413-422.
Topics: Adolescent; Agaricales; Female; Humans; Male; Nonprescription Drugs; Poland; Substance-Related Disorders
PubMed: 28512368
DOI: 10.13075/mp.5893.00245