• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.311-314
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• 2007

Paclitaxel (PTX) is an antineoplastic agent approved for the treatment of ovarian and breast carcinomas. However, the use of paclitaxel as an anticancer drug is limited by its extremely poor water solubility (below $0.3\;{\mu}g/mL$). Furthermore, it has very low bioavailability when administered orally because paclitaxel is a substrate of P-glycoprotein (P-gp) efflux pump. In this study, buccal delivery of PTX was investigated as one of the alternatives for PTX delivery. Ethanol and glyceryl monooleate (GMO) were selected as permeation enhancing agents to increase solubility and permeation across buccal mucosa of PTX. At the different concentrations of ethanol solution ($30{\sim}70\;w/w\;%$), PTX permeation was studied, followed effects of GMO in the concentration range of $2.5{\sim}25%$ with ethanol vesicle. The transbuccal ability of PTX was evaluated in vitro using Franz diffusion cells mounted with rabbit buccal mucosa. As a result, incorporation of PTX into ethanol vesicle with GMO significantly enhanced the PTX permeation in rabbit buccal mucosa. Particularly, the mixtures of ethanol:water:GMO at the ratio of 50:47.5:2.5 showed the most excellent enhancing ability. The results showed a promising possibility for buccal delivery of PTX.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.369-373
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• 2005

The objectives of the current work is to understand the factors impacting the formulation and performance of a Carbopol mucoadhesive buccal delvery system for a model peptide drug, $[D-Ala{^2},\;D-Leu{^5}]$enkephalin (DADLE, Mw=569.7) with comparable chemical and enzymatic stability. Specifically, in vitro buccal DADLE delivery from the cross-linked poly(acrylic acid) (PAA) hydrogel system was characterized. In addition, the influences of several penetration enhancers on the ex vivo buccal absorption of DADLE were also studied. In this study, the PAA hydrogels generally swell to 100% of their original weight in the phosphate pH 7.4 buffer. The water penetration into the PAA hydrogel occurred based on a zero-order kinetics for the first 60 min and steadily decreased afterwards. From the release study, it can be seen that the initial DADLE release was so rapid and the rate of release of DADLE decreased as the time elapsed. The porcine buccal tissue was found to be permeable to DADLE with a flux value of $0.07%/cm{^2}/hr({\pm}0.01\;SD)$. From the ex vivo diffusion study, it was found that sodium taurodihydrofusidate showed a greater degree of enhancement compared to the phospholipids with an Enhancement Ratio (ER) of 8.7 compared to 2.7 and 1.9 for didecanoylphosphatidylcholine and lysophosphatidylcholine, respectively. The work encompassed within this paper has demonstrated the feasibility of using the PAA hydrogel delivery system with its good mucoadhesive properties for the buccal delivery of peptides.

• Archives of Pharmacal Research
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• 제26권5호
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• pp.421-425
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• 2003

The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The permeation rate of [$^3 H$]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P＜0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [$^3 H$]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [$^3$H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

• Journal of Pharmaceutical Investigation
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• 제35권2호
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• pp.71-74
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• 2005

The aim of this study was to analyze characteristics of the barrier function of excised porcine buccal mucosa to the test compounds, estradiol, propranolol HCI, melatonin, and mannitol with a wide range of partition coefficient values. The permeability of melatonin was measured through frozen, stored, and fresh porcine buccal mucosa to examine the impact of storage conditions on the permeability of porcine buccal mucosa. The results demonstrated that the ex vivo permeability of the porcine buccal mucosa was greater for more lipophilic solutes, which was consistent with a series of molecules transported by passive transepithelial diffusion. The melatonin permeation profiles through frozen, stored, and fresh mucosa illustrated that damage was incurred by the freezing process of the mucosal tissue, leading to loss of the barrier function and thereby an increased permeation coefficient. It can be observed that the influence of compound lipophilicity on the association of the compounds with buccal mucosa was clear. The relationship between permeation coefficient and Log P values for the four compounds investigated demonstrated a proportional relationship, further confirming the importance of the lipophilicity of a compound to permeate the buccal mucosa. These results showed that the ex vivo porcine buccal mucosa model is a suitable tool to screen oral mucosal permeability.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.235.2-235
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• 2003

To develop the buccal delivery system of rhEGF for the treatment of buccal mucosal ulcer, polymer films and hydrogels were investigated. Methods: Hydrogels for thermosenstive sol/gel systems were prepared by the cold method (Schmolka, 1972). And mucoadhesive films were prepared by mixing sod. alginate/polycarbophil 974p. To find an optimum buccal mucosal adhesive gel or film, the gel strength of the poloxamer and sod. alginate/polycarbophil 974p hydrogels were determined by the Simple Rheology Method and their mucoadhesiveness were measured by the Instron (M 4400, Instron Co., U.S.A.) method. (omitted)

• Journal of Pharmaceutical Investigation
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• 제22권4호
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• pp.251-266
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• 1992

A major problem with the peptide-based drugs is that these drugs must generally be administered by injection. Therefore, there is considerable research interest in alternative routes of delivery, such as buccal, nasal, gastrointestinal route and etc. Site-specific drug delivery to the colon, as an alternative to parenteral drug delivery, is of interest for the delivery of peptide-based drugs as well as the delivery of low molecular weight drugs for the treatment of colonic disease, This review describes some considerations of colon-specific drug delivery using hydrogels.

• Archives of Pharmacal Research
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• 제26권8호
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• pp.659-665
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• 2003

We have studied the effect of rhEGF on the buccal mucosal ulcer healing. rhEGF was rapidly degraded upon incubation with the hamster buccal mucosal homogenates; The degradation of rhEGF was significantly inhibited by sodium lauryl sulfate (SLS). Eudispert hv hydrogel and Polycarbophil 974P hydrogel were prepared for rhEGF delivery and their mucoadhesiveness was measured by the $Instron^R$ method. The mucoadhesive force of Eudispert hv was significantly greater than that of Polycarbophil 974P. Moreover, rhEGF in Eudispert hv hydrogel remained stable for about 2 months. To evaluate the ulcer healing effect of rhEGF, the buccal mucosal ulcer was induced in golden hamsters using acetic acid. At 24 h after administration of rhEGF/Eudispert hv hydrogel, the ulcerous area was decreased compared with rhEGF solution and, as a result, the curative ratio was $36.8\pm5.68$%. By the addition of SLS (0.5%) to Eudispert hv hydrogel, the curative ratio increased 1.5 times. The mechanism of the action was probably due to a combination of protection of the drug against proteases present in mucosa and prolongation of the release of rhEGF from the formulation at the site of action.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권1호
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• pp.45-54
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• 2019

Background: Profound anesthesia with adequate duration is required in periodontal flap surgery, which involves the manipulation of both hard and soft tissues. The anterior middle superior alveolar (AMSA) injection may be an alternative to multiple injections required for this purpose in the maxilla. The present study aimed to assess the effectiveness of AMSA injection using computer-controlled local anesthetic delivery (CCLAD) system to anesthetize buccal hard tissue (BHT), buccal soft tissue (BST), palatal hard tissue (PHT), and palatal soft tissue (PST) around the maxillary teeth. Methods: Thirty-five patients who were indicated for open flap debridement in a whole maxillary quadrant were given AMSA injection using the CCLAD. The effectiveness of anesthesia was evaluated using subjective and objective parameters around each tooth. Supraperiosteal infiltrations were administered to complete the surgery wherever the AMSA injection was ineffective. Results: The AMSA injection was more effective on the palatal tissues than on the buccal tissues, as 94.14% of PST and 87.89% of PHT sites were anesthetized compared to 49.22% and 43.75% of BHT and BST sites, respectively. There was no significant difference in the frequency of anesthesia around the anterior and posterior teeth. The PHT was significantly more anesthetized (P = 0.003) in males than in females. Conclusions: The AMSA injection using CCLAD is highly effective on palatal tissues and could be used as a first-line anesthesia for periodontal flap surgery. However, its effect on buccal tissues is less predictable, with supraperiosteal infiltration often required to supplement the AMSA injection.

• Journal of Pharmaceutical Investigation
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• 제27권2호
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• pp.133-137
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• 1997

Buccal absorption test of omeprazole in human was performed to determine the permeability of the drug molecule through oral mucous membrane. Oral mucosal adhesive tablets of omeprazole were prepared by compressing the omeprazole with a mixture of sodium alginate and hydroxypropylmethyl cellulose (HPMC) as bioadhesive polymers, magnesium oxide (MgO) as a stabilizer and sodium carboxymethyl cellulose (Na CMC) or cros-carmellose sodium (Ac-Di-Sol) as disintegrants. The bioadhesive force, stability in saliva and release characteristics of the tablets were evaluated. Omeprazole was absorbed about 23% in 15 min through human buccal mucous membrane. Furthermore, omeprazole was stable in saliva for more than 8 hrs when MgO was added to the tablet as the amount of 2.5 fold of omeprazole. The release rate of omeprazole was increased with increasing the amount of sodium alginate in the tablet. From these results, it is suggested that tablets composed of [omeprazole/HPMC/sodium alginate/MgO/Ac-Di-Sol and/or Na CMC (20/6/24/50/10) (mg/tablet)] are potential candidate for buccal drug delivery system.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.113-118
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• 2010

Pharmaceutical technology has primarily focused on the development of the best dosage forms depending on the route of administration. The design of dosage forms is greatly influenced by the route of administration. Due to a variety of advantages such as avoidance of first-pass effect, abundant blood supply and easy access to the absorption site, the oral cavity has frequently been selected as a site for drug delivery. Since the oral cavity is relatively unique from the anatomical and physiological viewpoint, one should always consider these conditions when designing the drug delivery systems for the oral cavity. In this regard, the current review paper was prepared to summarize the essential features of the drug delivery systems utilized in the oral cavity, along with the introduction of various dosage forms developed to date.