Effects of HPMCAS MF on absorption of silybin from supersaturable self-nanoemulsifying drug delivery system / 中国中药杂志

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Formulation and in vitro evaluation of nateglinide microspheres using HPMC and carbopol-940 polymers by ionic gelation method

This study involves the design and characterization of Nateglinide [NAT] microspheres to enhance patient compliance. Ionic gelation technique was used to prepare Nateglinide Microspheres by using rate controlling polymers Carbopol-940 and Hydroxypropylmethyl cellulose [HPMC]. Shape and surface were evaluated with Scanning electron microscopy [SEM]. Percentage Yield, Particle size analysis, Encapsulating Efficiency, Micromeritic analysis, Fourier Transform Infra-Red Spectroscopy [FTIR], Differential Scanning Colorimetry [DSC] were done for characterization of Microspheres. Drug release studies were performed at pH 1.2 and 7.2 using USP dissolution type-2 apparatus and release rates were analyzed by the application of different pharmacokinetic models. The size of microspheres was found to be varied from 781 Micro m to 853 Micro m. Rheological studies proved excellent flow behavior while percentage yield was found to be varied from 72% to 79%. Absence of drug-polymers interactions was confirmed from FTIR and DSC results. The microspheres prepared with sodium alginate showed cracks while microspheres obtained from blend of Carbopol-940 plus sodium alginate were smooth and spherical. Maximum entrapment efficiency [71.4%] was achieved for Microspheres with Carbopol-940. The greater retardation in drug release was observed for microspheres containing Carbopol-940 and release pattern followed Higuchi kinetics model and negligible drug release was observed at pH 1.2

A clinical comparison between DisCoVisc and 2% hydroxypropylmethylcellulose in phacoemulsification: a fellow eye study

OBJECTIVE: This study sought to compare the effects and outcomes of two ophthalmic viscosurgical devices, 1.6% hyaluronic acid/4.0% chondroitin sulfate and 2.0% hydroxypropylmethylcellulose, during phacoemulsification. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that received phacoemulsification performed by the same surgeon using a standardized technique. Patients were randomly assigned to receive either 1.6% hyaluronic acid/4.0% chondroitin sulfate or 2.0% hydroxypropylmethylcellulose on the first eye. The other eye was treated later and received the other viscoelastic agent. Preoperative and postoperative examinations (5, 24 and 48 hours; 7 and 14 days; 3 and 6 months) included measurements of the total volume of the ophthalmic viscosurgical device, ultrasound and washout times to completely remove the ophthalmic viscosurgical device, intraocular pressure, central corneal thickness and best-corrected visual acuity. The corneal endothelial cell count was measured at baseline and at six months postoperatively. ClinicalTrials.gov: NCT01387620. RESULTS: There were no statistically significant differences between groups in terms of cataract density or ultrasound time. However, it took longer to remove 2.0% hydroxypropylmethylcellulose than 1.6% hyaluronic acid/ 4.0% chondroitin sulfate, and the amount of viscoelastic material used was greater in the 2.0% hydroxypropylmethylcellulose group. In addition, the best-corrected visual acuity was significantly better in the hyaluronic acid/ chondroitin sulfate group, but this preferable outcome was only observed at 24 hours after the operation. There were no statistically significant differences between the two ophthalmic viscosurgical devices regarding the central corneal thickness or intraocular pressure measurements at any point in time. The corneal endothelial cell count was significantly higher in the hyaluronic acid/chondroitin sulfate group. CONCLUSION: The ophthalmic viscosurgical device consisting of 1.6% hyaluronic acid/4.0% chondroitin sulfate was more efficient during phacoemulsification and was easier to remove after IOL implantation than 2.0% hydroxypropylmethylcellulose. In addition, the corneal endothelial cell count was significantly higher following the use of hyaluronic acid/chondroitin sulfate than with hydroxypropylmethylcellulose, which promoted an improved level of corneal endothelium protection.

Completion rates of anterior and posterior continuous curvilinear capsulorrhexis in pediatric cataract surgery for surgery performed by trainee surgeons with the use of a low-cost viscoelastic.

Context: Pediatric cataract surgery is traditionally done with the aid of high-molecular-weight viscoelastics which are expensive. It needs to be determined if low-cost substitutes are just as successful. Aims: The study aims to determine the success rates for anterior and posterior capsulorrhexis and intraocular lens (IOL) implantation in the bag for pediatric cataract surgery performed with the aid of a low-molecular-weight viscoelastic. Settings and Design: Nonrandomized observational study. Materials and Methods: Children less than 6 years of age who underwent cataract surgery with IOL implantation in the period May 2008–May 2009 were included. The surgeries were done by pediatric ophthalmology fellows. A standard procedure of anterior capsulorrhexis, lens aspiration with primary posterior capsulorrhexis, anterior vitrectomy, and IOL implantation was followed. Three parameters were studied: successful completion of anterior and posterior capsulorrhexis and IOL implantation in the bag. Results: 33 eyes of 28 children were studied. The success rate for completion was 66.7% and 88.2 % for anterior and posterior capsulorrhexis, respectively. IOL implantation in the bag was successful in 87.9%. Conclusions: 2% hydroxypropylmethylcellulose is a viable low-cost alternative to more expensive options similar to high-molecular-weight viscoelastics. This is of great relevance to hospitals in developing countries.

Development of meloxicam formulations utilizing ternary complexation for solubility enhancement

Meloxicam [an oxicam derivative], a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water [8 microg/ml], which directly influences the C[max], T[max], as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using p-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC [methocel IH], methylcellulose [400cps], PVP K30, HPMC [K[4]M], HPMC [50cps]. It is reported that when small amount of water soluble polymer is added to beta-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of beta-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility [90 microg/ml] of the drug and results in superior formulations of the drug by using beta-cyclodextrin blended with 0.12% w/w HPMC [Methocel IH]. Ternary complexation is a valuable tool for solubility enhancement of drugs

Enhanced local anesthetic action of mepivacaine from the bioadhesive gels

Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain. Among the many drug delivery systems, transdermal drug delivery has some advantages, as it provides controlled drug delivery for an extended period of time. To develop new gel formulations that have suitable bioadhesion, the bioadhesive force of hydroxypropyl methylcellulose [HPMC] was assessed using an auto-peeling tester. The effect of drug concentration on drug release from 2% HPMC gel was studied using synthetic cellulose membrane at 37 +/- 0.5°C. The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and 42°C. To increase the skin permeation of mepivacaine from HPMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug permeation was then examined in the modified Keshary-Chien cell. For the efficacy study, the anesthetic action of the formulated mepivacaine gel containing enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive forces increased. Increasing the drug concentration or temperature increased the drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancement of permeation. Based on the area under the efficacy curve of the rat tail flick test curve, mepivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased local anesthetic action compared to the control. For bioadhesive mepivacaine gels with enhanced local anesthetic action, mepivacaine gels containing penetration enhancer and vasoconstrictor could be developed with the bioadhesive polymer, HPMC

[Study and evaluation the influence of HPMC combination with different polymers in ketoprofen controlled release matrix tablets]

The controlled release of the drug is performed by trying to achieve to zero order kinetic mechanism from the dosage form. Zero-order kinetic mechanism means that drug release is separated from amount of the drug in a delivery system [the rate of released drug is constant during the time]. HPMC is Hydrophilic swellable polymer and widely used to control the release of drugs from matrix formulations, the release of drugs from their matrices depends on percentage of polymer in the matrices and its viscosity. In this study we investigate the applicability of HPMC combination with different polymers [PEG6000, Sodium alginate, Xanthan gum and PVA] for controlling the release of ketoprofen from matrix tablets. In drug release profiles, an initial rapid burst occurs in the first hour for matrices that consist of HPMC, then the release decrease during the time, it is not a suitable for Zero-order kinetic mechanism, but the initial rapid burst did not occur in the first hour for matrices that consist of HPMC combination with different polymers or HPMC polymers with various viscosities. The release during the time differs according to the type of studied polymer and the percentage of the two polymers and viscosity of the interested HPMC within the matrix. The kinetics of ketoprofen release was analyzed using different drug release models [zero order, first order, Higuchi, Korsmeyer and Peppas, Hixon and crowel], Zero order and Korsmeyer and Peppas equations were suitable for most of dissolution data from matrix tablets [0.95< R[2] <0.99]. The value of correlation factor R[2] according to zero order increases in combinations comparison to formulas that consist of HPMC alone

Formulation and in vitro evaluation of ofloxacin-ethocel controlled release matrix tablets prepared by wet granulation method: influence of co-excipients on drug release rates

Being controlled release dosage forms, tablets allow an improved absorption and release profiles of Ofloxacin. The fact that drugs with fine particles size can be compressed well after wetting, so in our research studies Ofloxacin controlled release matrix tablets were prepared by wet granulation technique. In order to investigate the potential of Ethyl cellulose ether derivatives as a matrix material, Ofloxacin formulations with different types and grades of Ethocel were prepared at several drug-to-polymer ratios. The method adopted for in vitro drug release studies was USP Method-1 [rotating Basket Method] by Pharma test dissolution apparatus using phosphate buffer 7.4 pH as a dissolution medium. Various Kinetic models were employed to the formulations for the purpose of determination of release mechanism. A comparative study was performed between the tested Ofloxacin-Ethocel formulations and a standard reference obtained from the local market. FI dissimilarity factor and f2 similarity factor were applied to the formulations for the checking of dissimilarities and similarities between the tested formulations and reference standard

Comparative results of gastric submucosal injection with hydroxypropyl methylcellulose, carboxymethylcellulose and normal saline solution in a porcine model / Resultados comparativos de injeção submucosa gástrica com hidroximetil celulose, carboximetilcelulose e soro fisiológico em modelo suíno

CONTEXT: Endoscopic mucosal resection is an established modality for excision of sessile lesions in the gastrointestinal tract. Submucosal fluid injection creates a cushion and may prevent thermal injury and perforation. OBJECTIVES: This blind study investigated the performance of three different solutions to create submucosal fluid cushions in porcine stomach. METHODS: Three solutions were injected in the stomach of nine pigs BR1: normal saline solution, carboxymethylcellulose 0.5 percent and hydroxypropyl methylcellulose 0.25 percent. In each pig, submucosal injections with 6 mL per test-solution were performed. One drop of methylene blue was added to all injections for better visualization. The time for the bleb to disappear was recorded. RESULTS: The overall median time of visible submucosal cushion was 37 minutes (range 12-60 min) for hydroxypropyl methylcellulose, 31 minutes for carboxymethylcellulose (range 10-43 min) and 19 minutes for normal saline solution (range 8-37 min). There was no statistically significant difference neither between normal saline solution and carboxymethylcellulose (P = 0.146) nor carboxymethylcellulose and hydroxypropyl methylcellulose (P = 0.119) but the median duration of hydroxypropyl methylcellulose was significantly longer than normal saline solution (P = 0.039). CONCLUSIONS: The length of hydroxypropyl methylcellulose submucosal fluid cushion is longer in comparison with normal saline solution. The median time for carboxymethylcellulose was not longer than normal saline solution. Hydroxypropyl methylcellulose, in the concentration of 0.25 percent, may be a durable alternative for submucosal injection.

CONTEXTO: A ressecção endoscópica mucosa é uma modalidade estabelecida para a excisão de lesões sésseis no trato gastrointestinal. A injeção de fluídos na submucosa cria uma coxim que pode prevenir lesão térmica e perfuração. OBJETIVO: Este estudo cego investiga o desempenho de três diferentes soluções para criar um coxim fluído submucoso no estômago suíno. MÉTODOS: Três soluções foram injetadas no estômago de nove porcos BR1: soro fisiológico, carboximetilcelulose 0.5 por cento e hidroxipropil metilcelulose 0.25 por cento. Em cada porco, injeções submucosas com 6 mL por solução-teste foram realizadas. Uma gota de azul de metileno foi adicionada a cada injeção para melhor visualização. O tempo de desaparecimento de cada coxim foi registrado. RESULTADOS: O tempo mediano total do coxim submucoso visível foi de 37 minutos (faixa 12-60 min) para hidroxipropil metilcelulose, 31 minutos para carboximetilcelulose (faixa 10-43 min) e 19 minutos para soro fisiológico (faixa 8-37 min). Não houve significância estatística entre soro fisiológico e carboximetilcelulose (P = 0.146), assim como entre carboximetilcelulose e hidroxipropil metilcelulose (P = 0.119), mas a duração mediana de hidroxipropil metilcelulose foi significativamente maior que a do soro fisiológico (P = 0.039). CONCLUSÃO: A duração do coxim submucoso com hidroxipropil metilcelulose é maior em comparação com o do soro fisiológico. O tempo mediano da carboximetilcelulose não foi maior que do soro fisiológico. A hidroxipropil metilcelulose, na concentração de 0.25 por cento, pode ser uma alternativa durável para injeção submucosa.

Formulation and in vitro evaluation of pH sensitive oil entrapped polymeric blended gellan gum buoyant beads of clarithromycin

A gastroretentive pH sensitive system has been a frontier approach to release the drug in controlled manner in stomach and duodenum. The aim of this study was to develop buoyant beads of gellan based, wherein, the oil was entrapped, blended with hydroxypropyl methyl cellulose or carbopol 934 in order to evaluate its potential for targeted sustained delivery of clarithromycin in the gastric region. Buoyant beads of gellan was developed by inotropic gelation technique using calcium carbonate as gas forming agent and the drug polymer dispersion was emulsified with mineral oil. The oil was entrapped and blended with hydroxypropyl methyl cellulose or carbopol 934. The developed beads were evaluated in terms of diameter,% floating, encapsulation efficiency, In vitro drug release, in vivo gastric residence efficacy and clarithromycine concentration in the mucosa of the experimental animal model. The scanning electron microscope photograph indicated that the prepared beads were spherical in shape and buoyancy, encapsulation efficiency and drug content obtained from all batches were satisfactory. Particle size and percentage buoyancy of the gel beads increased by raising the concentration of calcium carbonate. The formulation exhibited sustained release profile and was best fitted in the Peppas model with n < 0.45. Subsequent coating of microbeads exhibited zero-order sustained pattern of the drug release up to 8 hrs. Batch B4 showed comparatively better residence and the drug concentration in the gastric mucosa of the treated animals. The result provides evidence that the prepared optimized formulation may be used effectively for pH sensitive gastric targeted antibiotic such as clarithromycin

Preformulation compatibility study of aceclofenac with tablet excipients [natural and synthetic] using differential scanning calorimetry

Differential scanning calorimetry was used as a tool to study the tablet excipient-Aceclofenac interactions in order to assess their compatibility. Compatibility studies were carried on samples of 1:1 physical mixtures of the drug with various excipients [natural and synthetic] viz., Hydroxy propyl methyl cellulose, Ethyl cellulose, Chitosan, Eudragit, and Magnesium stearate as sustained release polymers and lubricant respectively at room temperature. Aceclofenac was found to be compatible with all the excipients viz. Hydroxy propyl methyl cellulose, Ethyl cellulose, Chitosan, Eudragit and Magnesium stearate

Mechanical properties and water vapour permeability of film from haruan [channa striatus] and fusidic acid spray for wound dressing and wound healing

Aerosol is a new dosage form for wound dressing and wound healing. Concentrate of aerosols which were prepared for wound dressing and wound healing will produced films after sprayed onto the surface of wounds. The aim of this study is to evaluate the mechanical and water vapour permeability properties of the films from the aerosol concentrates. Film forming dispersions contained Haruan extract and Fusidic acid as the active ingredients, hydroxypropyl methylcellulose [HPMC] as polymer and polyethylene glycol [PEG] 400, glycerin and propylene glycol as plasticizers. Haruan extract is used to promote healing and Fusidic acid is added in formula as antibiotic to prevent the infections. The films were prepared by using casting technique. Based on the results, it is concluded that films produced from Formula El, E2 and F4 possessed good elongation at break but low tensile strength. All Formula E, Formula F4 and F5 were permeable but Formula F5 was brittle and would peel off by themselves from the Petri dish

[ use of hydroxypropyl methylcellulose in controlling the release of sparingly soluble drug from tablets prepared using polyethylene glycol]

The purpose of this study is to investigate the possibility of preparing controlled release tablets for sparingly soluble drug, nicardipine hydrochloride NC, which is chosen as a model drug for this study and hydroxypropyl methylcellulose HPMC as an excipient for controlling the drug release from tablets prepared using PEG4000. The solid dispersion NC:PEG4000 was prepared by fusion method and evaluated using dissolution test, differential scanning calorimetry DSC, Infra red spectra, and X-ray diffraction. Although NC is sparingly soluble in water but it is dissolved and released rapidly from NC:PEG4000 solid dispersion at different ratios and more than 80% of the drug is released after 45 min. On the other hand, the release rate of NC is decreased significantly as HPMC ratio is increased. The present results confirm that adding HPMC in the ratio 60% to the NC tablet prepared with PEG4000 could produce controlled release tablets which are in full agreement with FDA requirements for controlled release systems

[Effects of plasticizers and surfactants on the film forming properties of hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets]

Hydroxy Propyl Methyl Cellulose [HPMC] 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium [DFS] tablets 25mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol [PEG] 400 and propylene glycol [PG]. The defect free selected formulations were further subjected for studying the effects of surfactants like Sodium Lauryl Sulphate [SLS] and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5%>0.5%>1.0% and for PG 1%> 4%> 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS+PEG-400 is in the order 0.3%< 0.5%< 0.1% and SLS+PG is in the order 0.5%< 0.1%< 0.3%. In case of Tween-80+PEG-400 the order is 0.3%< 0.5%< 0.1% and Tween-80+PG is in the order 0.3%< 0.1%< 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug-polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p

Formulation and characterization of nystatin gel

The main objective of this research is to develop and characterize a series of carbopol 934 (CP) hydroxypropyl methylcellulose (HPMC) and a combination of carbopol-HPMC as a gel base for topical delivery of nystatin. The drug level was held constant at 1.72% w/w and the level of propylene glycol which is used as a co-solvent and penetration enhancer was also kept constant at 2% w/w. The total level of the polymer was held constant at 1.5% w/w as a single polymer or combination of two polymers. The polymers combination selected were: carbopol 934 to HPMC at a ratio of 0:1, 1:0, 1:2, 2:1 and 1:1. The batch size was 500 g and triethanolamine was used to adjust the pH of the gel. The rheological study showed that formulation containing combination of 2 carbopol and 1 HPMC ratio gave the highest viscosity, and exhibited an apparent pseudoplastic thixotropic behavior. The diffusion study indicated that gel formulation containing carbopol-HPMC at a ratio of 2:1 gave the highest percent drug diffusion compared to formulation containing low carbopol to HPMC ratio, carbopol alone or HPMC alone. Both in-vitro release and rheological study indicated that carbopol-HPMC had the best gel strength, physical properties and ability to diffuse the drug than carbopol or HPMC alone. The results obtained in this study demonstrated that the combination of carbopol and hydroxypropyl methylcellulose can be used as a gel vehicle for nystatin topical application.

Development of time and pH dependent controlled release colon specific delivery of tinidazole

Tinidazole is used in treatment of amoebiasis and other protozoal infections in doses of 2.0 g/ day [60 mg/kg] for three days. In the present paper, controlled release formulation of tinidazole was developed with an objective to achieve colon specific drug delivery with reduced frequency of dosing, to minimize gastric side effects and thus to increase patient compliance. Matrix systems of tinidazole [500 mg] were prepared by using swellable and pH dependent polymers like hydroxypropyl methylcellulose [HPMC K4M and K15M] and eudragit [eudragit L-100 and S-100]. Prepared tablets were enteric coated in order to overcome variability in gastric emptying time and delay in the release, to reduce gastric side effects and to provide prolonged localized action in colon. Process of manufacture was optimized during the scale up studies. Bioavailability study [using parallel group design] was carried of on conventional marketed, developed uncoated and enteric coated tablets in healthy human volunteers. Bioavailability study showed that greater portion of tinidazole was released in the large intestine and drug level in plasma was above 4 micro g/mL in blood for 24 hours. From the results of this study it appears that, the proposed single enteric coated tinidazole [500 mg] tablet per day could be used in place of 3-4 doses of 500 mg tinidazole conventional tablet with better control of drug release for targeted drug delivery. In addition developed colon-specific drug delivery system [CDDS] was relatively inexpensive and easy to manufacture using conventional pharmaceutical coating technique

pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

Propranolol HC1, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15% were added to the matrices prepared by hydroxypropyl methylcellulose [HPMC] and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time [MDT] as well as similarity factor [f[2]] were calculated for all formulations. It was found that incorporation of 5 and 10% tartaric acid in tablet formulations with 30% HPMC resulted in a suitable pH-independent release profiles with significant higher f[2] values [89.9 and 87.6 respectively] compared to acid free tablet [58.03]. The other two acids did not show the desirable effects. It seems that lower pK[a] of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles

Percutaneous absorption of haloperidol from different gel polymers through rabbit, human and hairless-mouse skins

Haloperidol is a butyrophenone derivative used for the treatment of psychotic symptoms. This compound is rapidly and almost completely absorbed when taken orally, but the oral bioavailability is about 60% due to extensive first-pass metabolism in the liver. Dorsal rabbit, human and hairless-mouse skins were used to investigate the diffusion properties of haloperidol. The transdermal permeation across full-thickness skins is reported from three polymer gel formulations was investigated using improved Franz-diffusion cells. Gels were prepared containing haloperidol and hydroxypropylmethyi cellulose [HPMC], carbopol 940 and polyethylene glycol mixture. Steady-state flux was rapidly achieved. Zero-order release of haloperidol from these formulations was observed. HPMC was concluded to be a suitable base for a matrix formulation. The reported partition coefficients in this study for human rabbit and hairless-mouse were 0.004, 0.041 and 0.155 respectively. The mechanism of action of the preparations tested were probably due to structural modification of the skin [stratum cornium] or fluidization of the cell contents in the epidermal layer

Transdermal permeation of trimetazidine from nerodilol-based HPMC gel drug reservoir system across rat epidermis

To study the in vitro transdermal permeation of trimetazidine from hydroxypropylmethyl cellulose [HPMC] gel drug reservoir system using nerodilol as a penetration enhancer. An HPMC gel containing selected concentrations of nerodilol [0, 2, 4 or 5% w/v] and 2.5% w/v of trimetazidine was prepared, and subjected to in vitro permeation studies across rat epidermis. The amount of trimetazidine permeated at different time intervals [1, 2, 4, 8, 12, 18 and 24 h] was estimated, and the data were analyzed to calculate various permeation parameters. There was an increase in the amount of trimetazidine [8,719.7 +/- 153.3 micro g/cm[2]] permeated across the rat epidermis up to 24 h [Q[24]] with an increase in nerodilol concentration [5% w/v] in HPMC gel drug reservoir. However, no significant difference [p > 0.05] was observed in the amount of drug permeated [Q[24]] with 5% w/v of nerodilol when compared to that obtained with 4% w/v of nerodilol [8,484.5 +/- 165.8 micro g/ cm[2]]. Nerodilol, at a concentration of 4% w/v enhanced the flux of trimetazidine across rat epidermis by about 1.96 times when compared to control. The HPMC gel drug reservoir containing 4% w/v of nerodilol showed optimal transdermal permeation of trimetazidine