Evaluation of performance of co crystals of mefloquine hydrochloride in tablet dosage form.

OBJECTIVE: The objective of present investigation was to evaluate performance of cocrystals of Mefloquine Hydrochloride (MFL) in tablet dosage form. Our previous investigation showed significant effect of cocrystal formers on improving the solubility and dissolution rate of Mefloquine hydrochloride by cocrystallization method when prepared by solution cocrystallization method. MATERIALS AND METHODS: Prepared cocrystals of MFL with different ratio of cocrystal formers were incorporated in tablet dosage form and evaluated for micrometric properties, drug content, hardness, disintegration test, vitro dissolution studies and stability studies. Performance was compared with laboratory prepared tablet of MFL 250 mg. RESULTS: The considerable improvement in the dissolution rate was observed in case of cocrystals based tablets than pure MFL tablets. DISCUSSION AND CONCLUSION: So we can incorporate cocrystals in tablet dosage form to enhance in vitro and in vivo performance. To the best of our knowledge, this is the first report, cocrystals has been evaluated in tablet dosage form.

Crystal engineering to improve physicochemical properties of mefloquine hydrochloride.

BACKGROUND: Pharmaceutical cocrystallization is a promising alternative for improving the solubility and dissolution rate or manipulating other physical properties of active pharmaceutical ingredients. The objective of this investigation was to study the effect of cocrystallization with different cocrystal formers on physicochemical properties of mefloquine hydrochloride. METHOD: Cocrystals were prepared by solution crystallization method--mefloquine hydrochloride (414.8 mg, 1 mmol) and different cocrystal formers (1/2 mmol) were dissolved in 20 mL of ethanol with warming. Solution was cooled in ice bath for 6 hours. The crystals were isolated by filtration through a membrane (0.45 microm) and dried in the air. The pure drug and the prepared cocrystals were characterized in terms of saturation solubility, drug content, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, in vitro dissolution studies, and stability studies. RESULTS: The cocrystals showed enhanced solubility and dissolution rate. The cocrystals were found to be stable over the period of 6 months confirmed from stability studies. CONCLUSION: Cocrystals resist the conversion of anhydrous form of drug into its hydrate which is responsible for the drugs less solubility and dissolution rate.

Protective effect of Morus alba leaves on haloperidol-induced orofacial dyskinesia and oxidative stress.

Long-term treatment with haloperidol, a typical neuroleptic, induces neurodegeneration caused by excitotoxicity and oxidative stress, which play an important role in the development of orofacial dyskinesia. In the present investigation, an attempt has been made to examine the effect of a concomitant treatment of methanol extract of Morus alba Linn. (Moraceae) leaves (100-300 mg/kg, i.p.) and haloperidol (1 mg/kg, i.p.) on an animal model of tardive dyskinesia. Rats were treated for 21 days with haloperidol and Morus alba extract; vacuous chewing movements and tongue protrusions were counted. The extract attenuated the increase in vacuous chewing movements and tongue protrusions induced by haloperidol, which were quantified on day 22. The extract showed a marked effect on behavioral parameters altered by haloperidol treatment. Similar treatment with extract attenuated haloperidol-induced lipid peroxidation and nitrite and normalized superoxide dismutase, catalase, and protein in comparison to the control group. The results suggest a protective effect of Morus alba extract against haloperidol-induced orofacial dyskinesia and oxidative stress.

Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats.

Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg/kg) was studied on reserpine-induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg/kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg/kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine-induced orofacial dyskinesia and oxidative stress.

Effect of Morus alba L. (mulberry) leaves on anxiety in mice.

OBJECTIVE: The aim of the present work is to evaluate the anxiolytic effect of a methanolic extract of Morus alba L. leaves in mice. MATERIALS AND METHODS: The hole-board test, elevated plus-maze paradigm, open field test, and light/dark paradigm were used to assess the anxiolytic activity of the methanolic extract of M. alba L. Morus alba extract (50, 100, and 200 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were administered 30 min before the tests. RESULTS: The results showed that the methanolic extract of M. alba significantly increased the number and duration of head poking in the hole-board test. In the elevated plus-maze, the extract significantly increased the exploration of the open arm in similar way to that of diazepam. At a dose of 200 mg/kg i.p. the extract significantly increased both the time spent in and the entries into the open arm by mice. Further, in the open field test, the extract significantly increased rearing, assisted rearing, and number of squares traversed, all of which are demonstrations of exploratory behavior. In the light/dark paradigm, the extract produced significant increase in time spent in the lighted box as compared to vehicle. The spontaneous locomotor activity count, measured using an actophotometer, was significantly decreased in animals pretreated with M. alba extract, indicating a remarkable sedative effect of the plant. CONCLUSION: The results of the present study suggest that a methanolic extract of M. alba leaves may possess an anxiolytic effect.

Cardiotonic activity of aqueous extract of heartwood of Pterocarpus marsupium.

The present study was undertaken to evaluate cardiotonic activity of aqueous extract of heartwood of P. marsupium. This plant species contains 5,7,2-4 tetrahydroxy isoflavone 6-6 glucoside which are potent antioxidant and are believed to prevent cardiovascular diseases. Cardiotonic effect of aqueous extract of heartwood of P. marsupium was studied by using isolated frog heart perfusion technique (IFHP). Calcium free Ringer solution was used as vehicle for administration of aqueous extract of P. marsupium as a test extract and digoxin as a standard. A significant increase in height of force of contraction (positive inotropic effect) and decrease in heart rate (negative chronotropic effect) at a very low concentration (0.25 mg/ml) was observed with test extract as compared to the same dose of a standard digoxin. The present results indicated that a significant increase in height of force of contraction with decrease in heart rate was observed as the dose of test extract increased. The test extract produced cardiac arrest at 4 mg/ml, a higher concentration, as compared to standard, digoxin (0.5 mg/ml). Compared to digoxin, a drug with narrow therapeutic window, P. marsupium showed wide therapeutic window.

Formulation and Solid State Characterization of Nicotinamide-based Co-crystals of Fenofibrate.

The present investigation deals with formulation of nicotinamide-based co-crystals of fenofibrate by different methods and solid-state characterization of the prepared co-crystals. Fenofibrate and nicotinamide as a coformer in 1:1 molar ratio were used to formulate molecular complexes by kneading, solution crystallization, antisolvent addition and solvent drop grinding methods. The prepared molecular complexes were characterized by powder X-ray diffractometry, differential scanning calorimetry, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and in vitro dissolution study. Considerable improvement in the dissolution rate of fenofibrate from optimized co-crystal formulation was due to an increased solubility that is attributed to the super saturation from the fine co-crystals is faster because of large specific surface area of small particles and prevention of phase transformation to pure fenofibrate. In vitro dissolution study showed that the formation of co-crystals improves the dissolution rate of fenofibrate. Nicotinamide forms the co-crystals with fenofibrate, theoretically and practically.

Co-crystals: a novel approach to modify physicochemical properties of active pharmaceutical ingredients.

Crystal form can be crucial to the performance of a dosage form. This is especially true for compounds that have intrinsic barriers to drug delivery, such as low aqueous solubility, slow dissolution in gastrointestinal media, low permeability and first-pass metabolism. The nature of the physical form and formulation tends to exhibit the greatest effect on bioavailability parameters of water insoluble compounds that need to be given orally in high doses. An alternative approach available for the enhancement of drug solubility, dissolution and bioavailability is through the application of crystal engineering of co-crystals. The physicochemical properties of the active pharmaceutical ingredients and the bulk material properties can be modified, whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of co-crystals to modify physicochemical characteristics of active pharmaceutical ingredients along with the case studies. The intellectual property implications of creating co-crystals are also highly relevant.

Development of biodegradable starch microspheres for intranasal delivery.

Domperidone microspheres for intranasal administration were prepared by emulsification crosslinking technique. Starch a biodegradable polymer was used in preparation of microspheres using epichlorhydrine as cross-linking agent. The formulation variables were drug concentration and polymer concentration and batch of drug free microsphere was prepared for comparisons. All the formulations were evaluated for particle size, morphological characteristics, percentage drug encapsulation, equilibrium swelling degree, percentage mucoadhesion, bioadhesive strength, and in vitro diffusion study using nasal cell. Spherical microspheres were obtained in all batches with mean diameter in the range of above 22.8 to 102.63 mum. They showed good mucoadhesive property and swelling behaviour. The in vitro release was found in the range of 73.11% to 86.21%. Concentration of both polymer and drug affect in vitro release of drug.