Egg shell membrane as a substrate for optimizing in vitro transbuccal delivery of glipizide

Buccoadhesive gels for transbuccal delivery of glipizide were prepared using different bio-adhesive polymers. The gels were prepared by solution polymerization technique. An apparatus simulating the in vivo conditions of the mouth was designed in order to assess in vitro drug release kinetics of these gels. The gels were also evaluated for spreadability, buccoadhesive strength, swelling index, and viscosity. Maximum buccoadhesive strength was observed for formulation, F8 with good sustained release behavior, whereas viscosity and swelling index was highest for the formulation, F5 but with minimum buccoadhesive strength. The drug release kinetics followed Higuchi model with release mechanism being Fickian diffusion.     

Formulation and in Vitro–in Vivo Evaluation of Buccoadhesive Morphine Sulfate Tablets

Buccoadhesive controlled-release systems for the delivery of morphine sulfate were prepared by compression of hydroxypropyl methylcellulose (HPMC) with carbomer (CP), which served as the bioactive adhesive compound. The release behavior of systems containing 30 mg of morphine sulfate and various amounts of the two polymers was found to be non-Fickian. The adhesion force was significantly affected by the mixing ratio of HPMC and CP in the tablet, and the weakest adhesion force was observed at a ratio of 1:1 (HPMC:CP). Interpolymer complex formation was confirmed between HPMC and CP in acidic medium by turbidity, viscosity, and FT-IR measurements. The amount absorbed (percentage of the drug loaded) of the controlled-release buccoadhesive tablets in six healthy volunteers and was 30 ± 5%.     

喷昔洛韦眼用温度敏感原位凝胶的制备及评价（英文）

目的研制以普朗尼克F127为主要基质的喷昔洛韦制剂,以提高其眼部生物利用度。方法通过将HPMC K4M或卡波姆934P与普朗尼克F127复合使用,制备了喷昔洛韦的温度敏感原位凝胶。以胶凝温度、流变学、药物释放特性、药代动力学及眼部刺激性等为指标进行筛选,得到最优化处方。结果使用HPMC K4M或者卡波姆934P均能降低凝胶的胶凝温度,略微增加其粘度,延缓体系中药物的释放速率;药物释放为非Fick扩散;所有处方均未表现出眼部刺激或对角膜的损伤;含卡波姆934P和普朗尼克F127的凝胶体系的眼部生物利用度最高。结论含普朗尼克F127的喷昔洛韦制剂能够以滴眼液的形式给药,而达到眼部温度时可形成凝胶;体内外评价结果表明,含有HPMC K4M或卡波姆934P以及低浓度普朗尼克F127（12%）的喷昔洛韦制剂,提高了药物在眼部的生物利用度,是一种很有前景的眼部给药系统。     

Preparation and evaluation of procaine gels for the enhanced local anesthetic action

To develop the new procaine gel formulations with a suitable bioadhesive property, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer containing an enhancer and the local anesthetic action were evaluated. As the drug concentration in the gels and the temperature of surrounding solutions increased, the drug release increased. The activation energy of drug permeation was 4.35 kcal/mol for procaine. The effects of permeation enhancers on the permeation rate of drug through skin were studied using various enhancers, such as the glycols, the non-ionic surfactants, and the bile salts. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail-flick analgesimeter. From the area under the efficacy curve of the rat-tail flick tests, procaine gel containing polyoxyethylene 2-oleyl ether showed about 1.77-fold increase in analgesic activity compared with the control. These results support that the enhanced local anesthetic gels containing an enhancer could be developed using the bioadhesive polymer gels based on HPMC and poloxamer.     

Development of tretinoin gels for enhanced transdermal delivery.

To develop the new gel formulations that show sustained release for a period of time, the bioadhesive carbopol gels containing tretinoin were prepared. The release characteristics of drug from the carbopol gel were studied according to temperature, receptor medium and drug concentration. For the enhancement of its percutaneous absorption, some kinds of penetration enhancer were used. As the concentration of drug increased, the release of drug from the gel increased, showing concentration dependency. The increase of temperature showed the increased drug release, depending on the activation energy of permeation. Among the enhancers used such as the glycols and the non-ionic surfactants, polyoxyethylene 2-oleyl ether showed the best enhancing effect. The carbopol gels of tretinoin containing an enhancer could be developed for the enhanced transdermal delivery of drug.     

Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems

A reservoir-type transdermal delivery system (TDS) of bupranolol (BPL) was designed and evaluated for different formulation variables like gel reservoirs (made with anionic and nonionic polymers), rate controlling membranes and penetration enhancers on the drug release and in vitro skin permeation kinetics of the devices. Keshary-Chien type diffusion cells and pH 7.4 phosphate buffered saline (PBS) were used for drug release studies and excised rat skin was used as a barrier for permeation experiments. The release rate of BPL from nonionic polymer gel reservoirs [hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC)] was much higher than anionic polymer gel reservoirs [carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na CMC) and sodium alginate)]. Among different rate controlling membranes, Cotran-polyethylene microporous membrane demonstrated highest release rate for BPL than all other membranes. An optimized TDS formulation with HPC gel and Cotran-polyethylene microporous membrane was used to study the effect of penetration enhancers on the release and skin permeation rate of BPL from the TDS. Permeation rates of the devices containing 5% (w/v) pyrrolidone (PY) or 1-methyl-2-pyrrolidone (MPY) were about 3- and 1.5-fold higher than control (no enhancer, P<0.01) indicating PY to be better penetration enhancer for BPL than MPY. The permeation rates of devices containing partially methylated beta-cyclodextrin (PMbetaCD) and PMbetaCD-BPL complex were about 2.5- and 1.4-fold higher than control (P<0.01). Inclusion of 10 and 30% w/v propylene glycol (PG) in the devices increased the permeation rate by 1.4- and 1.8-fold higher than control (P<0.05). In conclusion, reservoir-type TDS of BPL was developed and penetration enhancers increased the skin permeation of BPL at 4-5 times higher levels than the desired target delivery rate.     

Correlation Between Rheological Properties and <Emphasis Type="Italic">In Vitro</Emphasis> Drug Release from Penetration Enhancer-Loaded Carbopol® Gels

Purpose

The aim of this study was to investigate the effect of commonly used penetration enhancers on the viscoelastic properties and in vitro drug release from topical gel formulations.

Methods

Three penetration enhancers, diethylene glycol monoethyl ether (Transcutol^®-P, TC), propylene glycol (PG), and 70 % ethanol were selected in this study. The non-steroidal anti-inflammatory drug diclofenac sodium (DNa) was used as a model drug. DNa gels were prepared using the gelling agent Carbopol^® 971P with or without different concentrations of the three penetration enhancers. Each gel formulation was characterized in terms of its viscoelastic properties (elastic or storage modulus G′ and viscous or loss modulus G″) using a controlled stress rheometer (CSR) and in vitro release using Franz diffusion cells.

Results

DNa gels containing TC, PG, and ethanol demonstrated a significant decrease in the viscoelastic properties compared to gels containing no penetration enhancers, and an enhancement in drug release. Gels containing TC at the highest tested concentration (40 %) exhibited the lowest viscoelastic properties and showed the highest enhancement in drug release. Both TC and ethanol showed a concentration-dependent effect in promoting steady-state flux values for DNa, unlike PG. DNa release kinetics from all gels followed super case II transport as fitted by the Korsmeyer–Peppas model.

Conclusions

Our results provide valuable insights into the mechanisms by which different penetration enhancers can modulate drug release from topical gels by altering the rheological properties of the gelling agent.

     

Formulation and optimization of duloxetine hydrochloride buccal films: in vitro and in vivo evaluation

Duloxetine hydrochloride (DH) is a serotonin–norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta^® 30?mg). The pharmacokinetic results showed that C_max for F2 was higher than the market product. In addition, ANOVA analysis showed that a T_max of F2 film was significantly lower, while, the AUC_0–72 of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.     

Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC–MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9–98.6%), (82.4–98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C_max and AUC_0–6?h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.     

Mechanisms of drug release in citrate buffered HPMC matrices

Few studies report the effects of alkalizing buffers in HPMC matrices. These agents are incorporated to provide micro-environmental buffering, protection of acid-labile ingredients, or pH-independent release of weak acid drugs. In this study, the influence of sodium citrate on the release kinetics, gel layer formation, internal gel pH and drug release mechanism was investigated in HPMC 2910 and 2208 (Methocel E4M and K4M) matrices containing 10% felbinac 39% HPMC, dextrose and sodium citrate. Matrix dissolution at pH 1.2 and pH 7.5 resulted in complex release profiles. HPMC 2910 matrices exhibited biphasic release, with citrate increasing the immediate release phase (<60 min) and reducing the extended release. HPMC 2208 matrices were accelerated, but without the loss of extended release characteristics. Studies of early gel layer formation suggested gel barrier disruption and enhanced liquid penetration. pH modification of the gel layer was transitory (<2 h) and corresponded temporally with the immediate release phase. Results suggest that in HPMC 2910 matrices, high initial citrate concentrations within the gel layer suppress particle swelling, interfere with diffusion barrier integrity, but are lost rapidly whereupon drug solubility reduces and the diffusion barrier recovers. These Hofmeister or osmotic-mediated effects are better resisted by the less methoxylated HPMC 2208.     

In vitro/in vivo studies on a buccal bioadhesive tablet formulation of carbamazepine

A buccoadhesive controlled-release system for delivery of carbamazepine (CBZ) was prepared by compression of hydroxypropyl methylcellulose (HPMC) and carbomer, incorporating a penetration enhancer, sodium glycodeoxycholate (GDC). The release behaviour of systems containing CBZ and various amounts of the two polymers with and without GDC was found to be non-Fickian. Formation of an interpolymer complex between HPMC and carbomer was confirmed in acidic medium by turbidity, viscosity and FT-IR measurements. Addition of the drug to the buccoadhesive formulation reduced the adhesion force significantly (p < 0.1). GDC did not have any effect on bioadhesion. Permeability of bovine buccal mucosa to CBZ was determined using Ussing diffusion chambers [1]. In vivo interaction between the tablet and tissue was examined histologically as well as by scoring mucosal irritation. Histological changes observed in the buccal epithelium after 4 h contact with the tablets containing GDC recovered completely within 24 h after removal. No measurable plasma level of CBZ was obtained either in the absence or presence of GDC.     

Development of lidocaine gels for enhanced local anesthetic action

In relieving local pains, lidocaine, one of ester type local anesthetics, has been used. To develop the lidocaine gels of enhanced local anesthetic effects, hydroxypropyl methylcellulose (HPMC) based bioadhesive polymer gel containing an enhancer was formulated. As the drug concentration in the gels increased up to 3%, the permeation rate of drug linearly increased, thereafter reaching a plateau. As the temperature of surrounding solutions increased, the permeation of drug increased. The activation energy of drug permeation was 3.29 kcal/mol for lidocaine. The permeation rate of drug through skin was studied using various enhancers, such as glycols, non-ionic surfactants, and bile salts. Among the enhancers studied, diethylene glycol showed the greatest enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail-flick analgesimeter. In the area under the efficacy curve (AUEC) of the rat-tail flick tests, lidocaine gel containing diethylene glycol showed about 3.89-fold increase in analgesic activity compared with the control. The addition of vasoconstrictor in the gels prolonged the analgesic effects. The result of this study supports that the bioadhesive gel with efficient anesthetic effect could be developed using HPMC with combination of enhancer and vasoconstrictor.     

Development of prilocaine gels for enhanced local anesthetic action

Prilocaine, one of local anesthetics, has been used for regional pain relief. When applied as an ointments or creams, it is hard to expect their effects to last for long time, because they are easily removed by wetting, movement and contacting. For more comfortable and better application, we developed a prilocaine gel system using a bioadhesive polymer, carboxymethyl cellulose (CMC). For suitable bioadhesion, the bioadhesive force of various polymers was tested using an auto-peeling tester. The bioadhesive force of various types of CMC such as 100MC, 150MC and 300MC, was 0.0264, 0.0461 and 0.0824 N, at 1.5% concentration, respectively. The CMC-300MC gels showed the most suitable bioadhesive forces. The effect of drug concentration on drug release was studied from the prepared 1.5% CMC gels using a synthetic cellulose membrane at 37 ± 0.5°C. As the concentration of drug increased, the drug release increased. The effects of temperature on drug release from the 1.0% prilocaine gels were evaluated at 27, 32, 37 and 42°C. As the temperature of the drug gels increased, drug release increased. The enhancing effects of penetration enhancers such as pyrrolidones, non-ionic surfactants, fatty acids and propylene glycol derivatives were studied. Among the enhancers used, polyoxyethylene 2-oleyl ether was superior. The anesthetic effects were studied by a tail flick analgesic meter. In the rat tailflick test, 1.0% prilocaine gels containing polyoxyethylene 2-oleyl ether showed the most prolonged local analgesic effects. The results support the view that prilocaine gels with enhanced local anesthetic action could be developed using CMC bioadhesive polymer.     

In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films

Background and the purpose of the study

Sertraline hydrochloride is a selective serotonin reuptake inhibitor principally used in the treatment of major depressive disorder. To maintain the therapeutic plasma drug concentration of the drug for prolonged period, the transdermal drug delivery has been chosen as an alternative route of drug delivery. The pharmacokinetic properties of sertraline hydrochloride make it suitable for transdermal delivery. The purpose of the study was to investigate the effect of polymers and penetration enhancers on the transdermal delivery of the drug in order to improve its therapeutic efficacy.

Methods

In the preparation of films, Eudragit RL 100, Eudragit RS 100, hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose were used as polymers. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, water vapor transmission rate and drug release. The films exhibiting higher rates of drug release were subjected to study the effect of oleic acid and propylene glycol as penetration enhancers on skin permeation of sertraline hydrochloride. In vivo and skin irritation studies were performed for the optimized film.

Results

Films containing Eudragit RL 100, Eudragit RL 100 and HPMC showed the highest drug release of 94.34% and 96.90% respectively in a period of 42 hrs. The release data fitted into kinetic equations, yielded zero-order and fickian mechanism of drug release. There was a two-fold increase in skin permeation of sertraline hydrochloride in the presence of penetration enhancers in the film. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rabbit skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The in vivo study revealed a constant plasma concentration of drug for long periods and the films containing penetration enhancers had achieved adequate plasma levels of the drug.

Conclusions

The obtained results indicated the feasibility for transdermal delivery of sertraline hydrochloride using eudragit RL 100 and HPMC.     

Preparation and evaluation of bioadhesive dibucaine gels for enhanced local anesthetic action

In relieving local pains, dibucaine, one of ester type local anesthetics, has been used. In case of their application such as ointments and creams, it is difficult to expect their effects for a required period of time, because they are easily removed by wetting, movement and contacting. To develop suitable bioadhesive gels, the bioadhesive force of hydroxypropyl cellulose (HPC) was tested using auto-peeling tester. The effect of drug concentration on drug release was studied from the prepared 2% HPC-HF gels using synthetic cellulose membrane at 37 ± 0.5°C. We investigated the enhancing effects on drug permeation into skins, using some kind of enhancers such as the glycols, the non-ionic surfactants, the fatty acids, and the propylene glycol derivatives. Anesthetic effects of dibucaine gels containing polyoxyethylene 2-oleyl ether were measured by tail flick analgesic meter. The bioadhesive force of various types of HPC such as GF, MF, and HF, was 0.0131, 0.0501, and 0.1346 N, at 2% HPC concentration, respectively. The HPC-HF gels showed the highest bioadhesive force. As the concentration of HPC-HF increased, the drug release increased. As the temperature increased, the drug release increased. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. According to the rat tail flick test, 1% drug gels containing polyoxyethylene 2-oleyl ether showed the prolonged local anesthetic effects. In conclusion, the dibucaine gel containing penetration enhancer and vasoconstrictor showing enhanced local anesthetic action could be developed by using the bioadhesive polymer, HPC.     

Effect of natural penetration enhancers on dermal delivery of hydrocortisone acetate

The purpose of the research work was to develop microemulsion (ME) of hydrocortisone acetate (HCA) using natural penetration enhancers and to determine its possibility in effective dermal delivery. Eucalyptus oil, clove oil and lemon grass oil were selected as natural penetration enhancers and pseudo-ternary phase diagrams were plotted using Tween 80 as surfactant and ethanol as cosurfactant. ME of each penetration enhancer was optimized using three factors, three levels Box–Behnken design, with independent variables as penetration enhancer, Tween 80 and ethanol. Formulations were assessed for percentage drug release as dependent variable. Response of these formulations decreased as the concentration of oil ranged from high to low and the response showed positive effect with increase in concentration of Tween 80 and ethanol. The globule size of optimized batches of eucalyptus oil, clove oil and lemon grass oil were found to be 226.1, 129.04 and 818.9 nm respectively. Optimized batches of MEs were then incorporated in carbopol 940 to form ME based gel without affecting their structure. Ex vivo permeation studies showed that amount of drug permeated from ME based gels was less than ME formulation indicating greater retention of HCA into skin layers. Retention of drug in skin layers both dermis and epidermis was higher for all three natural penetration enhancer. Hence natural penetration enhancers can be used for effective delivery of topical corticosteroids to the skin for improved treatment of several skin diseases and can be a better choice over synthetic penetration enhancers in terms of safety.     

Formulation and in vitro evaluation of prednisolone buccoadhesive tablets

In this research, the effect of mucoadhesive polymers such as hydroxyl propyl methyl cellulose (HPMC) with viscosity grade 60 and 500 mPas, sodium carboxy methyl cellulose (NaCMC) and carbopol 934 (Cp 934) alone or in combination with each other on the release profile of prednisolone was studied and mucoadhesion strength of these buccoadhesive formulations was evaluated. The results showed that the release of prednisolone from HPMC with viscosity grade 60 mPas and Cp 934 alone was fast and their mucoadhesion strengths was low. On the other hand, the release rates of prednisolone from the HPMC viscosity grade 500 mPas and NaCMC and mucoadhesion strengths were moderate and suitable. The results showed that with different blends of HPMC viscosity grade 500 mPas or NaCMC and Cp 934 with increasing in HPMC or NaCMC/Cp 934 ratio a remarkable decrease in the rate of drug release and an appreciable increase in the mucoadhesion strength was observed. Except from the formulations prepared with HPMC viscosity grade 60 and 500 mPas, other formulation had more fluctuations in release profiles and their kinetics of release were not fitted to zero order model.     

Formulation, characterization, and in vitro evaluation of bioadhesive gels containing 5-Fluorouracil

The objective of this study was to prepare and evaluate in vitro the bioadhesive gels of 5-Fluorouracil (FU) for the treatment of oropharyngeal cancer. In preformulation study, the physicochemical interactions between FU and polymers were investigated by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, and differential scanning calorimetry (DSC). According to FTIR, XRD, and DSC studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. The gel formulations containing FU were prepared by using Poloxamer 407, HPMC K 15 M, and Gantrez S-97 (polymethylvinylether-co-maleic anhydride). The formulations contained Poloxamer 407 (16-18% w/w) either alone or in combination with HPMC K 15 M and Gantrez S-97. The bioadhesiveness of the gels was found to increase with increasing proportion of HPMC K 15 M and Gantrez S-97. In vitro release studies indicated that release could be sustained up to 8 hr. The permeability coefficients (Kp) of gel across cellulose membrane and buccal mucosal membrane were 1.06 x 10(-4) cm/s and 3.94 x 10(-5) cm/s, respectively, and differed significantly ( p < 0.05). Increasing temperature increased the drug release by increasing drug diffusion despite increase in viscosity. The pH of the release medium showed a very slight effect on the release of FU. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as non-Fickian diffusion.     

Transbuccal permeation, anti-inflammatory activity and clinical efficacy of piroxicam formulated in different gels

In attempts to avoid the systemic side effects of piroxicam (PC) (e.g. gastrotoxicity), several buccal gel formulations containing PC were prepared and their effects on the characteristics of the drug permeation through rabbit buccal mucosa in-vitro were evaluated using a Franz-type diffusion cell. The general rank order of the total flux of 0.5% PC from gels was found to be: hydroxypropylmethylcellulose (HPMC, 2.5%) > hydroxypropylcellulose (HPC, 2.5%) >or= sodium alginate (Na alg., 7%) > methylcellulose (MC, 3%) > hydroxyethylcellulose (HEC, 1.5%) > carbopol 934 (Carb. 934, 1%) >or= sodium carboxymethylcellulose (NaCMC, 2%) > pluronic F-127 (PF-127, 20%) > polyvinyl alcohol (PVA, 10%). The effect of various penetration enhancers 1% sodium lauryl sulphate (NaLS), 3% sodium deoxycholate (NaDC), 3% sodium tauroglycocholate (NaTGC) on the rate of permeation across the excised buccal mucosa (of 0.5% PC in gels prepared using 3% MC, 2.5% HPMC or 7% Na alg. base) and histology of the buccal epithelium was also investigated. Pharmacodynamic evaluation of the anti-inflammatory activity of PC in these gel formulations (containing 3% NaDC as an enhancer) was carried out using the kaolin-induced rat paw oedema method. The results obtained indicated that PC administered in 7% Na alg. or 2.5% HPMC gel bases was significantly more effective than the 3% MC gel and oral drug solution in suppressing oedema formation in rats. Comparative clinical studies were conducted in patients with post-operative dental pain and oedema following maxillofacial operations. The results revealed that 7% Na alg. and 2.5% HPMC gel formulations applied to the buccal mucosa were slightly better than or equally effective to the orally administered commercial product (Feldene Flash) tablet) in reducing pain level, swelling and tenderness within a period of 4 days. These findings suggest that PC (0.5%) administered in the buccal gel may present a potential therapeutical use as a strong anti-inflammatory and analgesic agent.     

Formulation,Characterization, and In Vitro Evaluation of Bioadhesive Gels Containing 5-Fluorouracil

The objective of this study was to prepare and evaluate in vitro the bioadhesive gels of 5-Fluorouracil (FU) for the treatment of oropharyngeal cancer. In preformulation study, the physicochemical interactions between FU and polymers were investigated by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, and differential scanning calorimetry (DSC). According to FTIR, XRD, and DSC studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. The gel formulations containing FU were prepared by using Poloxamer 407, HPMC K 15 M, and Gantrez® S-97 (polymethylvinylether-co-maleic anhydride). The formulations contained Poloxamer 407 (16–18% w/w) either alone or in combination with HPMC K 15 M and Gantrez® S-97. The bioadhesiveness of the gels was found to increase with increasing proportion of HPMC K 15 M and Gantrez® S-97. In vitro release studies indicated that release could be sustained up to 8 hr. The permeability coefficients (Kp) of gel across cellulose membrane and buccal mucosal membrane were 1.06 × 10^?4 cm/s and 3.94 × 10^?5 cm/s, respectively, and differed significantly (p < 0.05). Increasing temperature increased the drug release by increasing drug diffusion despite increase in viscosity. The pH of the release medium showed a very slight effect on the release of FU. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as non-Fickian diffusion.