DEVELOPMENT OF MUCOADHESIVE DELIVERY OF CHLORZOXAZONE POLYETHYLENE GLYCOL SOLID DISPERSION

ABSTRACTObjective: Chlorzoxazone (CLZ) is centrally acting skeletal muscle relaxant. It is insoluble in water, so employed for the formation of solid dispersions(SD) as a means to enhance the dissolution rate, and carrier selected was polyethylene glycol 6000 (PEG 6000).Methods: The SDs were prepared by different methods and characterized by in vitro drug release, drug content, fourier transform infraredspectroscopy (FTIR), differential scanning calorimetry, powder X-ray diffraction. All the SD showed dissolution improvement compare to pure drug.These techniques revealed distinct loss of drug crystallinity in the formulation accounting for enhancement in dissolution rate. The SD methodsshowing best in vitro drug release profile were selected in the further development of mucoadhesive buccal patches. A buccal patch has been developedusing two mucoadhesive polymers, i.e. hydroxyl propyl methyl cellulose K4M and carbopol 974. The patches were evaluated for the physicochemical,mechanical and drug release characteristics. The optimized patches showed good mechanical and physicochemical properties to withstand theenvironment of the oral cavity. The in-vitro permeation study showed that patches could deliver drug to the oral mucosa for a period of 8 hrs.Results: The results indicate that suitable bioadhesive buccal patches with good permeability could be prepared. The batches FH4 and FC4 showed81.95% and 79.97% permeated through goat mucosa membrane in 8 hrs. The physicochemical interactions were investigated by FTIR, showed noany evidence of interactions and were present in an unchanged state. The stability study for SD and buccal patch carried out revealed that were stablefor a period of 3-month.Conclusion: Phase-solubility studies indicate significantly increase in solubility. The optimized buccal patches showed good mechanical andphysicochemical properties to withstand environment of the oral cavity.Keywords: Solid dispersions, Chlorzoxazone, Dissolution studies, Buccal patch, In vitro permeation studies

Synthesis and evaluation of analgesic, anti-asthmatic activity of (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 ones

Abstract Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2 , 4 , 12 , 14 , and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy's hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2 , 4 , 7 , 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2 , 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents

Application of Design of Experiment for Polyox and Xanthan Gum Coated Floating Pulsatile Delivery of Sumatriptan Succinate in Migraine Treatment

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR205 and xanthan gum. 32 experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study

Application of Design of Experiment for Floating Drug Delivery of Tapentadol Hydrochloride

The aim of the present study was to apply design of experiment (DOE) to optimize floating drug delivery of tapentadol hydrochloride. Tapentadol hydrochloride is a synthetic opioid used as a centrally acting analgesic and effective in both experimental and clinical pain. The half-life of the drug is about 4 hours and oral dose is 50 to 250 mg twice a day. For optimization 32 full factorial design was employed for formulation of tapentadol hydrochloride tablets. Sodium bicarbonate was incorporated as a gas-generating agent. Combination of polymers Xanthan gum and Locust bean gum was used to achieve controlled release effect. The concentration of polymers was considered as the independent variables and dependent variables were floating lag time and swelling index of the tablets. From the factorial batches, it was observed that formulation containing combination of 20% sodium bicarbonate and 10% citric acid shows optimum floating ability whereas the formulation containing 20% Xanthan gum and 28% Locust bean gum shows optimum sustained drug release pattern with adequate floating

Pharmaceutical equivalence of gabapentin tablets with various extragranular binders <b>Pharmaceutical equivalence of gabapentin tablets with various extragranular binders</b>

Gabapentin is a high-dose drug widely used as an oral anti-epilepticagent. Due to high crystalline and has poor compaction properties it is difficult to form tablets by direct compression. The aim of this study was to develop gabapentin tablets, pharmaceutically equivalent to the reference product Neurontin (marketed in USA). Gabapentin 800mg tablets were produced by wet granulation by keeping intragranular binder as well as its concentration constant and by changing with various extragranular binders with its concentration (A = PVPK 30, B = HPMC 15 cps, C = Kollidon VA 64, D =Klucel EXF).The tablet having no weight, thickness and hardness variation and having appropriate, friability as well as disintegration profile were coated with a 3% film coating solution .Seven formulations F1 (A in lower concentration) F2 (A in higher concentration), F3 (B in lower concentration) and F4 (B in higher concentration), F5 (C in lower concentration), F6 (C in higher concentration), F7 (D in lower concentration) were formulated. Among them F6 demonstrated adequate hardness, friability, disintegration, uniformity of content, and total drug dissolution after 45minutes. The dissimilarity factor (f1) is 5.93 and the similarity factor (f2) is 67.85. So F6 was found to be equivalent to Neurontin.Gabapentin is widely used as an oral anti-epileptic agent. However, owing to its high crystallinity and poor compaction properties, it is difficult to form tablets of this drug by direct compression. The aim of this study was to develop gabapentin tablets, pharmaceutically equivalent to the brand-name pioneer product Neurontin® (marketed in USA). Gabapentin 800mg tablets were produced by wet granulation with a constant concentration of intragranular binder and a varying concentration of extragranular binders (A = polyvinylpyrrolidone K30, B = hydroxypropylmethylcellulose 15 cps, C = Kollidon VA64, D =Klucel EXF). The tablets that did not vary in weight, thickness or hardness and had appropriate friability and disintegration profiles were coated with a 3% film-coating solution. Seven formulations F1 (A 3%), F2 (A 6%), F3 (B 3%), F4 (B 6%), F5 (C 3%), F6 (C 3%) and F7 (D 3%) were prepared. Among these, F6 exhibited adequate hardness, friability, disintegration, uniformity of content and total drug dissolution after 45minutes. Comparing the F6 dissolution profile with that of the brand-name tablets, the difference factor (f1) was 5.93 and the similarity factor (f2) 67.85. Hence, formulation F6 was found to be equivalent to Neurontin®. <i>Keywords</i>: Dissolution. Gabapentin. Tablet. Binder. Pharmaceutical equivalence

Antihyperglycemic, antistress and nootropic activity of roots of <i style="">Rubia cordifolia</i><i style=""> </i>Linn

987-992Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain γ-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract

Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology

Clonazepam (CLZ) is an anticonvulsant benzodiazepine widely used in the treatment of epilepsy. CLZ is a BCS Class II drug and its bioavailability is thus dissolution limited. The objective of the present study was to prepare solid dispersions (SDs) of CLZ by various techniques, using the amphiphilic carrier Gelucire 50/13 in various proportions, to increase its water solubility. Drug-polymer interactions were investigated by Fourier-transform infrared (FTIR) and UltraViolet (UV) spectroscopy. The SDs were characterized physically by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). A phase solubility study was performed and the stability constant (Ks) was found to be 275.27, while the negative Gibbs free energy (ΔGo tr) indicated spontaneous solubilization of the drug. The dissolution study showed that the SDs considerably enhanced the dissolution rate of the drug. The FTIR and UV spectra revealed no chemical incompatibility between the drug and Gelucire 50/13. XRD patterns and the DSC profiles indicated the CLZ was in the amorphous form, which explains the improved dissolution rate of the drug from its SDs. Finally, mouth dissolving tablets (MDTs) were prepared from the optimized batches (kneading method) of solid dispersion, using crospovidone and Doshion P544 resin as superdisintegrants. The tablets were characterized by in-vitro disintegration and dissolution tests. The study of the MDTs showed disintegration times in the range 32.0±0.85 to 20.0±1.30 sec and dissolution was faster than for the commercial preparation. In conclusion, this investigation demonstrated the potential of solid dispersions of a drug with Gelucire 50/13 for promoting the dissolution of the drug and contributed to the understanding of the effect of a superdisintegrant on mouth dissolving tablets containing a solid dispersion of a hydrophobic drug

Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl β-Cyclodextrin Inclusion Complexes

Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15–19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpβ-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpβ-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin