Hydroxypropyl Methylcellulose K4M Research Articles

DESIGN AND EVALUATION OF INTRAGASTRIC BUOYANT TABLETS OF VENLAFAXINE HYDROCHLORIDE

Objective: The present study was undertaken to prolong the release of orally administered drug. The aim is to formulate, develop, and evaluate theintragastric buoyant tablets of venlafaxine hydrochloride, which releases the drug in a sustained manner over a period of 12 hrs. Different formulationswere formulated using the polymers Carbopol 934 P, xanthan gum, hydroxypropyl methylcellulose (HPMC K100M) with varying concentration ofdrug: Polymer ratio of 1:1, 1:1.5, 1:2, in which sodium bicarbonate acts as gas generating agent, and microcrystalline cellulose as a diluent.Methods: The tablets were prepared by direct compression and evaluated for tablet thickness, weight variation, tablet hardness, friability, in vitrobuoyancy test, in vitro drug release and Fourier transform infrared spectroscopy. Formulations were evaluated by floating time, floating lag time and in vitro drug release. Dissolution profiles were subjected for various kinetic treatments to analyze the release pattern of drug.Results: It was found that drug release depends on swelling, erosion, and diffusion, thus following the non-Fickian/anomalous type of diffusion.Formulation F8 was considered as an optimized formulation for gastro retentive floating tablet of venlafaxine hydrochloride. The optimizedformulation showed sustained drug release and remained buoyant on the surface of the medium for more than 12 hrs. As the concentration of HPMCK100M increases in the formulation the drug release rate was found to be decreased. The optimized formulation was subjected for the stability studiesand was found to be stable as no significant change was observed in various evaluated parameters of the formulation.Conclusion: It can be concluded that floating drug delivery system of venlafaxine hydrochloride can be successfully formulated as an approach toincrease gastric residence time, thereby improving its bioavailability.Keywords: Venlafaxine hydrochloride, Intragastric buoyant, Floating drug delivery systems, Hydroxypropyl methyl cellulose K100M, Carbopol 934 P,Xanthan gum.

FORMULATION AND EVALUATION OF SIMVASTATIN GASTRORETENTIVE DRUG DELIVERY SYSTEM

Objective: The aim of this study was to formulate and evaluate gastro retentive drug delivery system (GRRDS) using an effervescent approach for simvastatin.Methods: Floating tablets were prepared using directly compressible polymers hydroxypropyl methylcellulose (HPMC) K100M, HPMC K4M and carboxymethylcellulose sodium (NaCMC). The prepared tablets were subjected to pre-formulation studies like Compressibility index, Hausner ratio and post compression parameters like buoyancy/floating test and In vitro dissolution study.Results: Drug-excipient compatibility studies performed with the help of FTIR instrument indicated that there were no interactions. The DSC thermogram of the formulations revealed that crystalline form of simvastatin existed in the formulation which was confirmed by X-ray powder diffraction. Dissolution studies indicated that there was a decrease in the drug release with an increase in the polymer viscosity. The tablets prepared with low-viscosity grade HPMC K4M exhibited short Buoyancy Lag Time and floated for a longer duration as compared with formulations containing high viscosity grade HPMC K100M. The ‘n’ value for dissolution studies for all the formulations was found to be in the range of 0.647 to 0.975 indicating non-Fickian or anomalous drug transport. Conclusion: The drug release rate and floating duration of tablets depended on the nature of the polymer and other added excipients. The release rate of the drug can be optimized by using different ratios of polymers and other excipients. The formulation F8 achieved the optimized batch and complied with all the properties of the tablets.

Formulation and characterization of mucoadhesive controlled release matrix tablets of captopril

The purpose of this study is to characterize controlled release matrix tablets of captopril and to find out the physicochemical properties that have an effect on the mucoadhesion process. The hydrophilic matrix tablets contain captopril, microcrystalline cellulose, barium sulfate, ascorbic acid, ethylcellulose N100, hydroxypropylmethylcellulose K15M, talc, magnesium stearate and colloidal silicon dioxide. The physicochemical properties of the formulations have been characterized using confocal microscopy, contact angle, and scanning electron microscopy. The potential mucoadhesion capabilities of the formulations were assessed measuring the surface free energy, the polar and dispersive forces, the spreading coefficients, the surface roughness, and the network structure of the hydrophilic matrix tablets. The results show that when the concentration of HPMC K15M increases, the spreading coefficients of polymer over mucus and mucus over polymer are more positive, thus increasing the contact between the matrix tablets with the mucus layer. The formulation that contains 15% of HPMC K15M is the formulation that presents a greater swelling capacity, a greater increase in surface roughness, and larger pores within the matrix. This formulation has a higher chain mobility and more free macromolecular chains able to diffuse in the mucus layer. Therefore, this formulation has the greatest potential mucoadhesion capability.

APPLICATION OF NOVEL NATURAL POLYMER FOR CONTROLLING THE RELEASE OF FENOVERINE FROM CONTROLLED RELEASE MATRIX TABLETS

Objective: To explore a novel natural polymer, pullulan for controlling the release of fenoverine from matrix tablets and to elucidate the release kinetics of fenoverine from pullulan and HPMC matrices.Methods: In this study we formulated monolithic matrix tablets containing of fenoverine as controlled-release tablets by direct compression using pullulan, HPMC (Hydroxypropyl methyl cellulose) K4M and HPMC K100M polymers and evaluated for hardness, thickness, friability, weight variation drug content, in vitro drug release characteristics and FTIR (Fourier transform infrared spectroscopy) and DSC (Differential scanning calorimetry) study.Results: All the formulations showed compliance with pharmacopoeial standards. FTIR and DSC study indicated the absence of interaction between fenoverine and excipients. The formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The results of dissolution studies indicated that the formulation F5 [drug to polymer 1: 0.35] exhibited highest % cumulative drug release of 96.82±0.75 % at the end of 12 h. Optimised batch F5 showed super case II transport mechanism and followed zero order release kinetics. Short-term stability studies of the optimized formulation indicated that there were no significant changes observed in hardness, drug content and in vitro dissolution studies at the end of three months period. Similarity factor f2 was found to be 89, which indicated similar dissolution profiles before and after stability study.Conclusion: Based on above results we conclude that pullulan can be used as a polymer for retarding the release of drug from matrix formulations.Keywords: Pullulan, Fenoverine, Hydroxypropyl methyl cellulose, Controlled release, In vitro

Influence of HPMC K100LV and Compritol® HD5 ATO on Drug Release and Rheological Behavior of HPMC K4M Matrix Tablets

The objectives of this study were to develop once-a-day oral controlled-release tablets of quetiapine fumarate (QF) and to determine the effect of polymer type, viscosity grade, polymer ratio, and polymer rheological properties on the rate of QF release from hydroxypropyl methylcellulose (HPMC) matrix tablets. Tablets were prepared from low-viscosity-grade HPMC K100LV (K100LV), high-viscosity-grade HPMC K4M (K4M), Compritol® HD5 ATO (PEGylated glyceryl behenate (PGB)), and binary combinations of these polymers. In vitro drug release from all tablets was evaluated over 24 h. In vitro drug release studies revealed that formulations containing K100LV/K4M and PGB/K4M at a ratio of 170:70 resulted in similar release profiles which extended for 24 h (f2 > 50). QF release kinetics followed either diffusion, anomalous transport, case II transport, or super case II transport, as fitted by the Korsmeyer-Peppas model. Tablet swelling and erosion studies were consistent with dissolution profiles. A linear relationship between % swelling and % QF released was observed in tablets containing K4M alone or in combination with K100LV or PGB, indicating the direct role of polymer swelling in controlling the mechanism of drug release. The viscoelastic properties of single and binary polymeric gels made with the three polymers (K100LV, K4M, and PGB) corroborated the in vitro release studies of QF tablets. Our results provide evidence that blending polymers with different viscosities and hydrophilicities can result in unique matrices with tunable release profiles.

Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.

Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol® 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol® 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm2, while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm2. N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

Formulation development and Evaluation of immediate and sustained release Bilayer Tablets Containing Amitriptyline HCl and Pregabalin for the treatment of Neuropathic Pain

The objective of proposed study was to prepare Bilayer tablet comprising Amitriptyline HCl (AMT) and pregabalin (PGB) for effective treatment of neuropathic pain. AMT was formulated as immediate release (IR) layer using disintegrants such as starch whereas PGB was formulated as sustained release (SR) layer using polymers hydroxypropyl methyl cellulose (HPMC) K100M for increasing with a view to deliver the drug at sustained manner in gastrointestinal tract and consequently into systemic circulation. Tablet blends were evaluated through various pre-compression tests, compressed by wet granulation method and evaluated. As disintegrant, starch at 14.70% concentration produced excellent results by immediately releasing AMT to exert its anti-depression and other additional beneficial effects. K100M grade of HPMC produced excellent SR efficiency at 1: 1 drug-polymer ratio whereas extended of the dosage form for long-lasting effect of the therapeutic agent. Final formulation released 98.92% drug in 45 min and 97.27% drug in 12 h, in vitro from respective layers. Pre-compression and post-compression parameters of optimized IR layer comprising AMT and SR layer comprising PGB exhibit satisfactory results. Bilayer tablet of AMT and PGB may prove to be very effective as a combination therapy for the treatment of neuropathic pain by sequential release of the drug.

Preparation and in vitro-in vivo evaluation of acyclovir floating tablets.

In the current study, floating dosage form containing acyclovir was developed to increase its oral bioavailability. Effervescent floating tablets containing 200 mg acyclovir were prepared by direct compression method with three different rate controlling polymers including Hydroxypropyl methylcellulose K4M, Carbapol 934, and Polyvinylpyrrolidone. Optimized formulation showed good floating properties and in vitro drug release characteristics with mean dissolution time and dissolution efficacy of about 4.76 h and 54.33%, respectively. X-ray radiography exhibited that the tablet would reside in the stomach for about 5 ± 0.7 h. After oral administration of floating tablet containing 200 mg acyclovir, the Cmax, Tmax, and AUC0–∞ of optimized gastroretentive formulation were found to be 551 ± 141 ng/mL, 2.75 ± 0.25 h and 3761 ± 909.6 ng/mL/h, respectively.

VARIOUS FORMULATION VARIABLES EFFECTING FLOATATION BEHAVIOUR OF SINGLE UNIT GASTRORETENTIVE CAPSULES OF OFLOXACIN

<p><strong>Objective: </strong>Objective of the present study was to prepare simple single unit gastro-retentive capsules of ofloxacin with the aim to have the gastric retention of the system for longer periods of time (12h) and to study the effect of various polymers on floating behaviour of such single unit gastro-retentive capsules of ofloxacin.</p><p><strong>Methods: </strong>The method used for the preparation of gastro-retentive capsules was a simple physical blending of various low-density hydrophilic polymers alone and in combination with hydrophobic polymers and filling into capsules. These capsules were then subjected to <em>in vitro</em> floatation and matrix integrity study in 0.1N HCl using static volume beaker method and the United States pharmacopoeia (USP) type II dissolution apparatus method at 100rpm.</p><p><strong>Results: </strong>Two grades of hydroxypropyl methylcellulose (HPMC) K4M and K15M used were found suitable for the purpose. Results showed that increase in HPMC level increased colloidal gel barrier strength along with matrix integrity with consequently improved buoyancy. Lactose which was added as release rate modifier decreased matrix integrity and buoyancy. Eudragit a hydrophobic polymer was added so as to have intact, the buoyant formulation for 12 h with desired drug release characteristics. The addition of eudragit enhanced matrix integrity and floatation time to certain levels but higher levels showed negative results. Floatation time of more than 16 h was observed in the formulations containing 2:1 ratio of HPMC K15M and eudragit respectively. 3<sup>2</sup> factorial design was used to study the effect of various formulation variables on buoyancy and matrix integrity. Formulations containing zero level of HPMC were found buoyant for more than 12 h with all levels of eudragit S100 (i.e.,-1, 0,+1 level). It was also observed that matrix integrity consequently buoyancy increased with increase in eudragit with all levels of HPMC.</p><p><strong>Conclusion: </strong>The study concludes that eudragit S100 a hydrophobic polymer increased floatation time of the formulated capsules with all the three levels of HPMC K15M, but at the same time eudragit level should not exceed HPMC, while lactose a release rate enhancer decreased matrix integrity/floatation time of the formulated capsules.</p>

Transbuccal delivery of betahistine dihydrochloride from mucoadhesive tablets with a unidirectional drug flow: in vitro, ex vivo and in vivo evaluation.

ObjectiveBetahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of Ménière’s disease, undergoes extensive first-pass metabolism and suffers from short biological half-life. The aim of the present work was to develop and estimate controlled release mucoadhesive buccal tablets of BH.2HCl with a unidirectional drug flow to overcome this encumbrance.MethodsA direct compression method was adopted for preparation of the tablets using mucoadhesive polymers like guar gum, hydroxypropyl methyl cellulose K4M, sodium carboxymethyl cellulose and their combinations. The tablets were coated from all surfaces except one surface with a solution of 5% (w/v) cellulose acetate and 1% (w/v) dibutyl phthalate. Different permeation enhancers like 2% sodium deoxycholate, 2% sodium cholate hydrate (SCH) and 5% menthol were tested. Swelling index, ex vivo residence time, mucoadhesion strength, in vivo testing of mucoadhesion time, in vitro dissolution and ex vivo permeation were carried out. Furthermore, compatibility and accelerated stability studies were performed for the drug excipients. Finally, drug bioavailability of the BH.2HCl-optimized buccal mucoadhesive formulation was compared with that of the orally administered Betaserc® 24 mg tablet in six healthy male volunteers.ResultsFormulation F10, which contained a combination of 35% guar gum and 5% sodium carboxymethyl cellulose, exhibited long adhesion time, high adhesion strength and diminished irritation to volunteers and showed zero-order release kinetics. SCH produced a significant enhancement in permeation of BH.2HCl across buccal mucosa. BH.2HCl-optimized buccal mucoadhesive formulation showed percentage relative bioavailability of 177%.ConclusionThe developed mucoadhesive tablets represent a promising alternative for the buccal delivery of BH.2HCl.

Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release

Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70 mg/tablet) and high (170 mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.

Design, Formulation and Evaluation of an Oral Gel from Punica Granatum Flower Extract for the Treatment of Recurrent Aphthous Stomatitis.

Purpose: Recurrent aphthous stomatitis is a disease with unknown etiology that's mostly treated symptomatically and has no definite cure. Pomegranate (Punica granatum) flowers have been used as medicinal herb that due to its antimicrobial, antioxidant, anti-inflammatory, analgesic and healing effects, has been useful in treatment of oral aphthous. Therefore, we decided to formulate a mucoadhesive gel with pomegranate flower extract to reduce the need for corticosteroid therapy in patients. Methods: Pomegranate flowers are extracted by percolation method. Several formulations with different amounts of carbomer 934, sodium carboxymethylcellulose (SCMC) and hydroxypropyl methylcellulose K4M were prepared and the condensed extract was dispersed in polyethyleneglycol (PEG) 400 and added to gel bases. Then the formulations underwent macroscopic and microscopic studies. The formulations that passed these tests successfully were studied through assay tests using spectrophotometry in 765 nm, drug release from mucoadhesive gel using cell diffusion method, viscosity test, mucoadhesion test and accelerated stability test. Results: The phenolic content of pomegranate flower dried extract was found to be 212.3±1.4 mg/g in dried extract. The F4-F6 formulations contains carbomer 934, SCMC, pomegranate flower extract, PEG 400, potassium sorbate and purified water passed all above tests. Conclusion: The F4 formulation had higher viscosity and mucoadhesion values due to its higher carbomer 934 and SCMC content. Since F4, F5 and F6 had no significant variation in drug release, the F4 formulation was chosen as the superior formulation because of proper appearance and uniformity, acceptable viscosity, mucoadhesion and stability in different temperatures.

FORMULATION OF AN INSITU FORMING INJECTABLE SUSTAINED RELEASE SPONGE OF GRANISETRON HYDROCHLORIDE

The overall aim of this work was to develop sustained release parenteral drug delivery system involving formation of an insitu sponge of an anti-emetic drug typically co-administered inchemotherapy induced nausea and vomiting. The study involved formulation of the drug Granisetron Hydrochloride in a sponge forming gelatin matrix as a dry powder for reconstitution into a suspension to be injected into the body forming a sponge insitu intended to release the drug over a period of 5 days. The formulation was prepared by the method cryogelation and optimised using gelatin5% as a sponge forming polymer, crosslinking agent glutaraldehyde 0.3% , sustained release retardant Hydroxypropylmethyl cellulose K100M 1% (HPMC K100M) and suspending agent sodium carboxymethylcellulose 1% (NaCMC) to form a  solution intended to be administered subcutaneously.The formulation was evaluated for all prerequisites of parenteral and other parameters of gelatin matrix like swelling index, surface scanning microscopy .for injectable suspension, sedimentation study, particle size,zeta measurement, invitro drug release, and stability studies. The formulation was found tosterile, isotonic, having swelling index 88% and SEM 100-120 μm,particle size 0.765μm.with zeta potential-14.2 mV, swelling time was 10 min. The in vitro drug release was found to be over 93.20% in Simulated Body fluid pH 7.4 at 37°C over a prolong period of 5days The formulation was physically and chemically stable at accelerated conditions for period of 1 month.

Mathematical Optimization and Investigation on Polymeric Blend of Chitosan and Hydroxy Propyl Methyl Cellulose K4M for Sustained Release of Metronidazole

Background: Sustained release gastro retentive drug delivery systems enable prolonged and continuous input of the drug to the gastrointestinal tract and improve the bioavailability of medications that are characterized by the narrow therapeutic window. Aim: The objective of this study encompasses the application of the response surface approach in the development of pharmaceutically active hydrodynamically balanced system (HBS)-containing metronidazole (MN). Materials and Methods: Experiments were performed according to a 32 factorial design to evaluate the effects of gel forming polymers, low molecular weight chitosan, and medium molecular weight chitosan on the buoyancy and time taken for 60% drug release (t60%). The effect of the two independent variables on the response variables was studied by surface response curves and contour plots generated by the Minitab-17 software. Results: The drug-excipients interaction studies performed by differential scanning calorimetry revealed drug polymer compatibility, and hence, formulations were prepared by physical blending of MN and polymers by encapsulation into hard gelatin capsules. In vitro buoyancy study and drug release study in the gastric environment showed the efficacy of the HBS to remain gastro retentive (buoyant) for a longer period and simultaneously sustained the release of the drug. Conclusion: Thus, a conclusion might be brought forward that the present HBS could be an ideal system for stomach specific sustained delivery of MN and would be useful to patients where the prolonged therapeutic action on the infection site caused by microorganisms is required.

Development Optimization and In-vivo Evaluation of Swellable Gastroretentive Tablet by 32 Factorial Design

Aim: The present invention preferably relates to formulation and characterization of a swellable gastroretentive tablet comprising pregabalin to enhance its bioavailability and retention time in the stomach. Materials and Methods: Tablets were prepared by wet granulation method using hydroxypropyl methylcellulose (HPMC) K4M and Psyllium husk as swelling agents and all other excipients were used of pharmaceutical grade. Results and Discussions: The tablet showed mucoadhesion time, force and strength 7.5-12 h, 24-28 g and 2.35-3.62 N, respectively. Swelling index and drug release were found to be 216% and 99.2%, respectively. In-vivo imaging study and pharmacokinetic study showed retention of tablet in gastrointestinal tract of rabbit for 24 h and release up to 24 h. The results for stability study were also same as they were at the initial stages of the evaluation. The method was also found optimum and valid when it was optimized using design expert software. The data obtained was best fit into Korsmeyer–Peppas model indicating non-Fickian or anomalous release and as compared to other models as R2 value was found to be 0.9983. Conclusion: It can be concluded that using polymers such as HPMC K4M and Psyllium husk the objective of this study are meet. The probability value indicates model terms are significant. The probability value, i.e., P value found was also <0.0500. The desirability value was found 0.984 which is equal to 1. From desirability, it can also be concluded that results actually obtained matches with the software prediction, and hence, the formulation is also validated.

HPMC-based gastroretentive dual working matrices coated with Ca+ 2 ion crosslinked alginate-fenugreek gum gel membrane

Novel alginate-fenugreek gum (FG) gel membrane coated hydroxypropylmethylcellulose (HPMC) based matrix tablets were developed for intragastric quetiapine fumarate (QF) delivery by combining floating and swelling mechanisms. The effects of polymer blend ratios [HPMC K4M:HPMC E15] and citric acid contents on time taken for 50% drug release (t50%, min) and drug release at 8h (Q8h, %) were studied to optimize the core tablets by 32 factorial design. The optimized tablets (F-O) exhibited t50% of 247.67±3.51min and Q8h of 71.11±0.32% with minimum errors in prediction. The optimized tablets were coated with Ca+2 ions crosslinked alginate-FG gel membrane by diffusion-controlled interfacial complexation technique. The biopolymeric-coated optimized matrices exhibited superior buoyancy, preferred swelling characteristics and slower drug release rate. The drug release profiles of the QF-loaded uncoated and coated optimized matrices were best fitted in Korsmeyer-Peppas model with anomalous diffusion driven mechanism. The uncoated and coated tablets containing QF were also characterized for drug-excipients compatibility, thermal behaviour and surface morphology by FTIR, DSC and SEM analyses, respectively. Thus, the newly developed alginate-FG gel membrane coated HPMC matrices are appropriate for intragastric delivery of QF over a prolonged period of time with greater therapeutic benefits.

Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation

The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.

Formulation Development of Floating Microspheres of Cefditoren Pivoxel by 32 Factorial Design and in Vitro Characterization

Aim: The main objective of the present research work was to develop floating microspheres of cefditoren pivoxel (CP) to provide the delivery of the drug at a sustained rate. Materials and Methods: Floating microspheres of CP were prepared by solvent evaporation technique using hydroxypropyl methylcellulose (HPMC) K4M and ethyl cellulose as the rate controlling polymers. The optimization of formulation was carried out by 32 factorial design using two factors; a total amount of polymer (X1) and concentration of ethyl cellulose (X2) as independent variables. The formulated floating microspheres were characterized by evaluating its yield, particle size, encapsulation efficiency, in vitro drug release, buoyancy, surface morphology (scanning electron microscopy analysis). Results and Discussion: The optimized formulation (F6) showed 91.5 ± 1.35% of drug release after 12 h and 75 ± 0.92% of entrapment efficiency. All the formulations have good buoyancy which was floated over 12 h in the dissolution medium. Conclusion: It can be concluded from the study that floating microspheres of CP can be prepared successfully using HPMC K4M and ethyl cellulose as the rate controlling polymers.

Transdermal Delivery of Diltiazem Hydrochloride from Poloxamer-HPMC Gel: in vitro, ex vivo, and in vivo Studies

Background: Hypertension is the most common cardiovascular disease worldwide and number one cause of death. Its related morbidities also impose huge economic burdens on population. The aim of the present investigation was to prepare thermal gel of Diltiazem Hydrochloride (DTZ) with different ratios of Poloxamer 407 (PLM 407) and Hydroxypropyl methylcellulose K100M (HPMC K100M) and to characterize their in vitro parameters, ex vivo permeation and in vivo antihypertensive activity. Methods: Cold method was used to prepare thermal gel of DTZ. In vitro testing such as interaction study using FTIR and DSC method, bioadhesive strength was measured using modified balance method, in vitro release study performed using dialysis bag method. Ex vivo permeation study was carried out by using a cylindrical glass diffusion cell. Rabbit model was used to perform in vivo antihypertensive activity. Results: The FT-IR spectra and DSC thermograms demonstrated the absence of interaction between DTZ and selected polymers. Based on the results obtained from in vitro studies, formulation DT3 having 1% w/w of HPMC K100M and 25% w/w of PLM 407 was selected as optimized thermal gel. Among the permeation enhancers (PEs) used in this study (such as L-menthol, transcutol and isopropyl myristate (IPM) at 10% (w/w)) L-menthol present in gel formulation DTm showed highest flux of 355.234 μg/cm2/h across abdominal skin of rat. Rabbit group treated with DTm exhibited prolonged (up to 8 h) antihypertensive effect in normotensive rabbits compared to orally treated group. Conclusion: The optimized gel with L-menthol has a promising potential as an effective product in the treatment of hypertension and expected to provide a better alternative to oral DTZ formulations with improved patient compliance. Keywords: Anti-hypertensive activity, diffusion, flux, permeation enhancers, stratum corneum, thermal gel.

Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.

Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.