Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies

Abstract

In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.     

Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation

Bioadhesive buccal tablet formulations for delivery of nicotine into the oral cavity were developed. Carbomer (Carbopol)974P NF) (CP) and alginic acid sodium salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated into the formulations as a pH increasing agent. In vitro release and bioadhesion studies were performed on the developed tablets. In the formulations containing CP:HPMC, the NHT released increased with the increasing HPMC concentration whereas a decrease was observed with increasing HPMC concentration in formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05) but increased significantly with the increasing CP concentration (P>0.05). A decrease in pH of the dissolution medium to acidic values was avoided by incorporation of magnesium hydroxide into the formulations. The developed formulations released NHT for 8h period, and remained intact except for the formulation containing CP:HPMC at 20:80 ratio.     

Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: Preparation,rheological, textural,mucoadhesive and release properties

This study developed and examined the characterization of Benzidamine hydrochloride (BNZ) bioadhesive gels as platforms for oral ulcer treatments. Bioadhesive gels were prepared with four different hydroxypropylmethylcellulose (HPMC) types (E5, E15, E50 and K100M) with different ratios. Each formulation was characterized in terms of drug release, rheological, mechanical properties and adhesion to a buccal bovine mucosa. Drug release was significantly decreased as the concentration and individual viscosity of each polymeric component increased due to improved viscosity of the gel formulations. The amount of drug released for the formulations ranged from 0.76?±?0.07 and 1.14?±?0.01 (mg/cm²?±?SD). Formulations exhibited pseudoplastic flow and all formulations, increasing the concentration of HPMC content significantly raised storage modulus (G′), loss modulus (G″), dynamic viscosity (?′) at 37°C. Increasing concentration of each polymeric component also significantly improved the hardness, compressibility, adhesiveness, cohesiveness and mucoadhesion but decreased the elasticity of the gel formulations. All formulations showed non-Fickian diffusion due to the relaxation and swelling of the polymers with water. In conclusion, the formulations studied showed a wide range of mechanical and drug diffusion characteristics. On the basis of the obtained data, the bioadhesive gel formulation which was prepared with 2.5% HPMC K 100M was determined as the most appropriate formulation for buccal application in means of possessing suitable mechanical properties, exhibiting high cohesion and bioadhesion.     

In Vitro-In Vivo Evaluation of a Controlled Release Buccal Bioadhesive Device for Oral Drug Delivery

Purpose. To investigate the use of buccal bioadhesive device in targeting controlled drug delivery to the gastrointestinal tract. Methods. A three-leg crossover study was designed to evaluate the application of buccal bioadhesive device for providing controlled drug delivery to the gastrointestinal tract of a model drug cyanocobalamin in four healthy adult male beagle dogs. Results. In vitro dissolution studies using deionized water as the medium indicated that 100% of the drug was released within 15 min from a immediate release oral capsule formulation, whereas 90% of the drug was released within a period of 18 hrs from a buccal bioadhesive device formulation. Drug release from the buccal bioadhesive devices appeared to follow Higuchi's square root of time dependent model. The terminal half-life of the drug following I.V. administration in four dogs was found to be 16.4 ± 2.4 hrs. Following immediate release oral capsule administration of the drug C_max, t_max and bioavailability were 2333 ± 1469 ng/L, 2.5± 1.0 hrs and 14.1 ± 7.9%, respectively. Following buccal bioadhesive device administration of the drug C_max, t_max and bioavailability were 4154 ± 1096 ng/L, 11 ± 1.2 hrs and 35.8 ± 4.1%, respectively. Significantly higher bioavailability of the drug was observed with the buccal bioadhesive device administration when compared to the immediate release oral capsule. Conclusions. The buccal bioadhesive device appears to improve the oral bioavailability of cyanocobalamin by providing controlled delivery of the drug to the gastrointestinal tract.     

Histological and bioadhesion studies on buccal bioadhesive tablets containing a penetration enhancer sodium glycodeoxycholate

For many drugs, buccal route offers many advantages over conventional routes of delivery with an improved bioavailability due to the avoidance of degradation in the gastrointestinal tract and hepatic first-pass metabolism. However, the major limitation to buccal drug delivery is the permeability barrier in the buccal mucosa. Use of penetration enhancers appears to be a pertinent approach to increase the drug permeation through the buccal epithelium. Buccal bioadhesive tablet formulations enable a delivery with a plasma drug level of the desired therapeutic response for a defined period of time, and also provides a means of confining the drug and penetration enhancer to a defined region of the mucosa. In this study, a bioadhesive tablet formulation for buccal delivery was designed using a mixture of hydroxypropyl methylcellulose and carbomer, incorporated with a penetration enhancer, sodium glycodeoxycholate (GDC). In vitro bioadhesion property of the formulated tablet was examined and histological study was carried out to examine an in vivo interaction between the tablet and tissue. GDC did not affect the adhesiveness of the tablet which makes it an acceptable excipient for a buccal bioadhesive drug delivery system. Histological changes such as loss of upper cell layers and formation of vacuoles as well swelling in the cells were observed in the buccal epithelium, after 4 h contact with the tablets containing GDC. Studies on reversibility of the interaction are in progress.     

Bioavailability of morphine after administration of a new bioadhesive buccal tablet

A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration–time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the C_max of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found. © 1998 John Wiley & Sons, Ltd.     

Development and in vitro evaluation of buccoadhesive carvedilol tablets

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 +/- 0.4%) with the Higuchi model release profile and permeated 21.5 +/- 2.9% of the drug (flux 8.35 +/- 0.291 microg h(-1)cm(-2)) permeation coefficient 1.34 +/- 0.05 cm h(-1)) through porcine buccal membrane. BC3 formulation showed 1.62 +/- 0.15 N of peak detachment force and 0.24 +/- 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.     

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.     

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m^?1 S^?2 and more than 2.5 kg/3 cm², respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.     

Evaluation of polyoxyethylene homopolymers for buccal bioadhesive drug delivery device formulations

Our objective was to evaluate the application of polyoxyethylene homopolymers in buccal bioadhesive drug (BBD) delivery device formulations. The bioadhesive strength of four different molecular weight (MW) polyoxyethylene polymers was measured by Instronâ tensile tester using glass plate and bovine sublingual tissue as substrate surfaces. Several BBD device formulations containing polyoxyethylene polymer (MW 7,000,000) were prepared by direct compression and compression molding processes. The prepared BBD devices were evaluated for their elasticity, in vitro adhesion and drug release characteristics. The in vivo bioadhesion characteristics of a placebo compression molded device were examined in 3 adult healthy male beagle dogs. The bioadhesive strength of polyoxyethylene polymers appeared to be directly related to their molecular weights. When bovine sublingual mucosa or a glass plate was used as model mucosal substrate surface, the rank order of bioadhesive strength of different molecular weight polyoxyethylene polymers was similar. The bioadhesive strength of devices prepared by the compression molding process was greater than those prepared by direct compression, but the kinetics of drug release were independent of the process used for the preparation of the devices. The drug release and the bioadhesive strength of the similarly prepared device formulations appeared to be dependent on the drug:polymer ratios. The elasticity of the BBD devices prepared by compression molding was improved by the inclusion of polyisobutylene polymer in the formulations. When adhered to the oral cavity of the dogs, the compression molded placebo BBD device exhibited adhesion for at least 4 hours and appeared to show no signs of local irritation. In conclusion, BBD devices containing polyoxyethylene polymer (MW 7,000,000) can be prepared by direct compression or compression molding process in order to provide controlled drug release to the oral cavity while maintaining appropriate bioadhesive characteristics.     

Design of a dissolution apparatus suitable for in situ release study of triamcinolone acetonide from bioadhesive buccal tablets

A new and simple dissolution apparatus which is capable of evaluating the release of drug and bioadhesive properties of buccal tablets has been developed. The apparatus consists of a dissolution cell and an outer assembly. The cell has been designed to hold the chicken pouch membrane and bioadhesive tablet together and also to allow the dissolution medium to flow over them. The outer assembly is to provide adjustment of the angle of flow of the medium over the cell. The release study of triamcinolone acetonide from various bioadhesive buccal tablets containing different proportions of poly(acrylic acid-2.5-dimethyl-1,5-hexadiene) (PADH) and hydroxypropylmethyl-cellulose (HPMC) with the apparatus reveals that the bioadhesion of the tablet and the release of drug are influenced by the different proportions of polymers. With higher concentrations of PADH, the tablets disintegrate much more rapidly, leading to a faster release of the drug and they give better adhesion to the membrane. Tablets with higher concentrations of HPMC provide more prolonged release of the drug. However, they can be dislodged from the membrane more easily. The results produced by the apparatus concur with the predicted patterns.     

Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique

The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.     

Development of mucoadhesive patches for buccal administration of carvedilol

A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution.     

生物粘附性达那唑缓释栓剂的处方筛选与体外释放度考察

目的 :生物粘附性达那唑栓剂的处方筛选 ,并考察其体外释放规律。方法 :以羟丙甲基纤维素 (HPMC)为缓释材料 ,将等量聚乙二醇6000(PEG6000)和聚乙二醇600(PEG600)以熔融法制备含不同HPMC量的缓释栓剂 ,考察释放度与HPMC用量之间的关系。结果 :随着HPMC用量增加 ,栓剂释药减慢 ,当HPMC与PEG的比例为1∶6 5时 ,栓剂中药物在体外12h内缓慢释放 ,符合一级释放规律。结论 :生物粘附性骨架材料HPMC能延缓达那唑从栓剂中释放 ,当HPMC与PEG的比例为1∶6 5时栓剂能达到设计要求。     

Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin

Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new gastroretentive sustained release delivery system was developed with floating, swellable and bioadhesive properties. All these properties were optimized and evaluated. Various release retarding polymers like psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations were tried and optimized to get the release profile for 24 h. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro bioadhesion property. The in vitro drug release followed Higuchi kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. For the developed formulation, the value of n was found to be 0.5766 while for the marketed formulation the value was 0.5718 indicating the anomalous transport. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of ofloxacin. The similarity factor f2 was found to be 91.12 for the developed formulation indicating the release was similar to that of the marketed formulation (Zanocin OD). The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix. The bioadhesive property of the developed formulation was found to be significant (P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone.     

Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats

Abstract

The aims of this study were to prepare fine famotidine-containing floating-bioadhesive cooperative minitablets and to investigate the possibility of using those minitablets as a delivery system for promoting the oral bioavailability of famotidine. Nine minitablet formulations were designed using hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol 971P as bioadhesive materials and sodium bicarbonate (NaHCO₃) as gas formers. The prepared 3?±?0.02?mm minitablets were evaluated in terms of their swelling ability, floating behavior, bioadhesion test and in vitro release. The optimized minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w) and NaHCO₃ (10.00%, w/w) were found to float in 1?min and remain lastingly buoyant over a period of 8?h in vitro, with excellent bioadhesive properties (20.81?g) and sustained drug release characteristics (T_50%?=?46.54%) followed one-order model. In addition, plasma concentration–time profiles from pharmacokinetic studies in rats dosed with minitablets showed 1.62-fold (p?<?0.05) increased absorption of famotidine, compared to the market tablets XinFaDing®. These studies demonstrated that the multiple-unit floating-bioadhesive cooperative minitablets may be a promising gastro-retentive delivery system for drugs that play a therapeutic role in the stomach.     

Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism

Abstract

Context: Mucoadhesive buccal films containing three layers (mucoadhesive layer, nanosuspension containing layer and backing membrane) were incorporated with carvedilol nanosuspension.

Objective: Formulation and evaluation of nanosuspension incorporated mucoadhesive buccal films of carvedilol for bioavailability enhancement by avoiding first-pass metabolism.

Methods: Carvedilol-loaded nanosuspension was prepared by a precipitation–ultrasonication method with varying concentrations of the polymer. The formulation was analyzed for size, size distribution, surface charge and morphology. Optimized nanosuspension was incorporated into drug gel layer which was sandwiched between a mucoadhesive layer and a backing layer to form tri-layered buccal films. They were evaluated for their physical, mechanical and bioadhesive parameters followed by in vitro and in vivo studies.

Results and discussion: Nanosuspension showed a negative zeta potential (?17.21?mV) with a diameter of around 495 nm and a polydispersity index of 0.203. Nanosuspension incorporated drug gel layer (62.4% drug loading) was optimized to contain 3% HPMC and 50?mg Carbopol 934P. The mucoadhesive layer and the backing layer were optimized to contain 3% HPMC and 1% ethyl cellulose, respectively. In vitro drug release was 69% and 62.4% in 9?h across synthetic membrane and porcine buccal mucosa, respectively. In vivo studies conducted in rabbit model showed 916% increase in the relative bioavailability in comparison to marketed oral tablet formulation. The C_max and T_max of the prepared formulation increased due to increased surface area of drug and also by-passing hepatic metabolism.

Conclusion: The drug delivery system has been designed as a novel platform for potential buccal delivery of drugs having high first-pass metabolism.     

A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation

Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100 mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24 h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.     

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.     

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。