DEVELOPMENT OF FLOATING GASTRORETENTIVE DRUG DELIVERY SYSTEM BASED ON A NOVEL EXCIPIENT FOR METFORMIN HYDROCHLORIDE USING MIXTURE DESIGN

Objective: The present study aimed to develop a new SR metformin hydrochloride (MH) gastroretentive formulation with novel excipient (NE), which has better floatation and can be prepared with more simple pharmaceutical techniques for the treatment of diabetes Mellitus. Methods: A gastro-retentive floating matrix tablet (GFT) formulation of MH was prepared using various concentrations of PEO (Polyox WSR-303) and hydroxypropyl methylcellulose K100M (HPMC K100 M) and Floating agent (novel excipient) to achieve desirable TFT, FLT and drug release. The wet granulation method was selected using isopropyl alcohol as a binder for the preparation of tablets. D-optimal non-simplex mixture design was used for the selection of suitable polymer concentrations and floating agents. Release kinetics was used to determine the mechanism of drug release. Results: It was observed that GFT with optimum quantities of PEO, HPMC K100M, and the floating agent showed 100 % of drug release in 24h with FT up to 24h and minimum FLT of less than 2 min. Formulation with an in vitro release profile slower to the marketed sample was prepared. Conclusion: A sustained-release (GFT) of MH tablets using PEO, HPMC K100M, and an effervescent system was successfully prepared. A GFT formulation with an in vitro release profile slower to the marketed sample that releases MH for 24h may suitable for once-daily dosing can be prepared

Optimization of Chitosan and Cellulose Acetate Phthalate Controlled Delivery of Methylprednisolone for Treatment of Inflammatory Bowel Disease

Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD. Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 32 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD

Gellified Emulsion of Ofloxacin for Transdermal Drug Delivery System

Purpose: Ofloxacin is a fluoroquinolone with broad-spectrum antibacterial action, used in treatment of systemic and local infections. Ofloxacin is BCS class II drug having low solubility, high permeability with short half-life. The present work was aimed to design, develop and optimize gellified emulsion of Ofloxacin to provide site targeted drug delivery. Transdermal drug delivery will enhance the bioavailability of the drug giving controlled drug release. Methods: Transdermal drug delivery system was designed with gelling agent (Carbopol 940 and HPMC K100M), oil phase (oleic acid) and emulsifying agent (Tween 80: Span 80). Effect of concentration of gelling agent on release of drug from transdermal delivery was studied by 32 factorial design. Emulgel was evaluated for physical appearance, pH, drug content, viscosity, spreadability, antimicrobial activity, in- vitro diffusion study and ex-vivo diffusion study. Results: FE-SEM study of the emulsion batch B5 has revealed formation of emulsion globules of approximately size 6-8 µm with -11.2 mV zeta potential showing good stability for the emulsion. Carbopol 940 had shown greater linear effect on drug release and viscosity of the formulations due to its high degree of gelling. In-vitro diffusion study through egg membrane had shown 88.58±1.82 % drug release for optimized batch F4. Ex-vivo diffusion study through goat skin indicated 76.68 ± 2.52% drug release. Conclusion: Controlled release Ofloxacin emulgel exhibiting good in-vitro and ex-vivo drug release proving good antimicrobial property was formulated

Solubility enhancement, physicochemical characterization and formulation of fast-dissolving tablet of nifedipine-betacyclodextrin complexes

Este estudo teve por objetivo principal incrementar a dissolução do nifedipino, fármaco pouco solúvel em água, por meio de sua complexação com β-ciclodextrina e estudar o efeito do método de preparação sobre o perfil de dissolução in vitro. A razão estequiométrica, determinada por ensaio de solubilidade de fase, para a complexação de nifedipino por inclusão em β-ciclodextrina foi 1:1. O complexo binário foi preparado por diferentes métodos, sendo caracterizado utilizando-se difratometria de raios X (XRD), calorimetria diferencial de varredura (DSC) e espectroscopia no infravermelho com transformada de Fourier (FT-IR). Realizou-se estudo de solubilidade de saturação para avaliar o incremento da solubilidade do nifedipino. O complexo otimizado foi formulado em comprimidos de dissolução rápida preparados por compressão direta, nos quais se utilizaram os superdesintegrantes Doshion P544, amido pré-gelatinizado, crospovidona, amidoglicolato de sódio e croscarmelose sódica. Os comprimidos, que foram avaliados quanto à friabilidade, dureza, variação de peso, desintegração e dissolução in vitro, apresentaram taxa de dissolução superior à do nifedipino pura.The main objective of the study was to enhance the dissolution of nifedipine, a poorly water soluble drug by betacyclodextrin complexation and to study the effect of the preparation method on the in vitro dissolution profile. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of nifedipine with β-cyclodextrin was 1:1. Binary complex was prepared by different methods and was further characterized using XRD, DSC and FT-IR. A saturation solubility study was carried out to evaluate the increase in solubility of nifedipine. The optimized complex was formulated into fast-dissolving tablets by using the superdisintegrants Doshion P544, pregelatinized starch, crospovidone, sodium starch glycolate and croscarmellose sodium by direct compression. Tablets were evaluated for friability, hardness, weight variation, disintegration and in vitro dissolution. Tablets showed an enhanced dissolution rate compared to pure nifedipine

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

Formulation and in vitro evaluation of taste-masked oro-dispersible dosage form of diltiazem hydrochloride

O cloridrato de diltiazem é bloqueador do canal de cálcio geralmente indicado para o tratamento de angina e de hipertensão e é extensamente biotransformado devido ao metabolismo hepático. A formulação do cloridrato de diltiazem em orodispersão pode prover rápida liberação com maior biodisponibilidade. O sabor amargo do fármaco deve ser mascarado para ser formulado em forma palatável. No presente trabalho tentou-se mascarar o sabor pela técnica de complexação, com uma orodispersão, usando superdesintegrantes, como Doshio P544, crospivodina (CP) e glicolato de amido sódico (SSG). Os complexos de cloridrato de diltiazem com β-CD (razão molar 1:1) foram preparados por mistura, coevaporação, comoagem, liofilização e métodos de fusão. A solubilidade de fase mostrou estabilidade constante de 819,13 M-1. Os complexos de inclusão preparados foram avaliados com relação ao mascaramento do sabor e caracterizados por IV, Difração de Raios X e DSC. Empregando-se o fármaco complexado com β-CD, prepararam-se comprimidos dispersíveis e avaliaram-se os mesmos quanto à dureza, friabilidade, variação de peso, espessura, tempo de desintegração (DT), taxa de dissolução e sabor. Formulações com 4% de Doshion, 8% de CP e 4% de SSG mostraram DT de 0,54, 0,35 e 1,23 minutos, respectivamente.Diltiazem hydrochloride is a calcium channel blocker generally indicated for the treatment of angina and hypertension, and it is extensively metabolized due to the hepatic metabolism. Formulation of diltiazem hydrochloride into an oro-dispersible dosage form can provide fast relief with higher bioavailability. The bitter taste of the drug should be masked to formulate it in a palatable form. In the present work, an attempt was made to mask the taste by complexation technique, with a formulation into an oro-dispersible dosage form, using superdisintegrants Doshion P544, crospovidone (CP) and sodium starch glycolate (SSG). The complexes of diltiazem hydrochloride with β-CD (1:1 molar ratio) were prepared by kneading, co-evaporation, co-grounding, freeze-drying and melting methods. Phase solubility showed stability constant 819.13M-1. Prepared inclusion complexes were evaluated for taste masking and characterized by I.R, XRD, DSC. Using the drug β-CD complex, oro-dispersible tablets were prepared and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), dissolution rate and taste. Formulations with 4 % Doshion, 8 % CP and 4 % SSG showed DT of 0.54, 0.35 and 1.23 minutes, respectively

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