Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Study on Pharmacokinetics of Fentanyl Buccal Tablet in Beagle Dogs / 中国药房

OBJECTIVE： To establish a method for blood concentration determination of Fentanyl buccal tablet in Beagle dogs， and to study its pharmacokinetics. METHODS： A total of 6 Beagle dogs were given Fentanyl buccal tablet 1 tablet （675 μg/tablet， buccally）. The blood samples were collected 2， 5， 10， 15， 30， 45， 60， 90， 120， 240， 360， 480， 720 min after administration. After precipitated by methanol， LC-MS/MS method [the determination was performed on Agilent C18 column with mobile phase consisted of methanol-0.02％ formic acid aqueous solution （95 ∶ 5， V/V） at the flow rate of 0.5 mL/min. The sample size was 5 μL and the column temperature was 30 ℃. Mass spectrometric conditions： electrospray ionization source in the multiple reaction monitoring mode was used to detect ions， fentanyl citrate： m/z 337.1→188.0； carbamazepine （internal standand）： m/z 237.1→194.1] was used to determine the blood concentration of fentanyl citrate； the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS： The linear range of fentanyl citrate were 1.0-325.0 ng/mL（r＝0.998）； inter-day RSDs of precision test were lower than 5％ （n＝6）， and intra-day RSDs were lower than 6％ （n＝3）； average recoveries were （94.65±6.32）％-（99.21±3.24）％ （n＝6）. RSDs of matrix effect was lower than 15％ （n＝6）； RE of stability tests were within ±6.2％ （n＝3）. The pharmacokinetic parameters of Fentanyl buccal tablet in Beagle dogs included that tmax was （32.5±6.1） min； t1/2 was （211.8±47.4） min； cmax was （40.3±1.9） ng/mL； CLz/F was （0.006±0.001） L/（min·kg）； AUC0-720 min was （7 564.0±1 576.7） ng·min/mL（n＝6）. CONCLUSIONS： The method is simple， feasible and accurate. Fentanyl buccal tablet have good fast-release and slow-release biphasic release characteristics in Beagle dogs.

Study on Formulation of Xiqingguo Buccal Tablet / 中国药房

OBJECTIVE:To study the formulation of Xiqingguo buccal tablet,optimize the proportion and quantity of main materials. METHODS:Using appearance,hardness,dissolution and taste as investigation indexes,orthogonal design was adopted to optimize the proportion and quantity of main thinner(lactose,mannitol),wetting agent(ethanol),lubricant(magnesium stea-rate),flavoring agent(aspartame),and critical relative humidity was detected. RESULTS:By wet granulation,the optimal formu-lation were as follows as the ratio of lactose and mannitol was 1:3,ethanol volume fraction was 60%,the dosage of menthol, magnesium stearate,aspartame and orange essence was 0.4%,0.9%,2.0%,0.4%;it was proven that the total score of 3 batches of samples were 2.67,2.67,2.70 (RSD=0.65%,n=3),respectively. The critical relative humidity of granule was 60%. CON-CLUSIONS:The Xiqingguo buccal tablet prepared by optimal prescription meets the requirements.

The effects of Shixinyatong buccal tablets in patients after the extraction of mandibular third molar / 实用口腔医学杂志

Objective:To study the effects of Shixinyatong buccal tablets(SBT)in patients after the extraction of mandibular third molar.Methods:150 cases of patients were divided into 3 groups(n =50).After tooth extraction the patients in SBT,cephalosporin and control groups were given SBT at 0.6 g,4 times per day,cepholosporin 0.5 g,2 times per day and no drug respectively.At the 3rd and 5th day the patients were followed up and their local symptoms were scored.The data were statistically analyzed with SAS 9.0 soft ware.Results:Between SBT and cepholosporin or control group there was no statistical difference in demographic data and impac-tion types of the teeth(P >0.05).The total symptom integral,primary symptom integral,minor symptoms,wound pain,redness, swelling degree and oral odor in SBT group were lower than those in control group(P 0.05)in the total symptom integral,primary symp-tom integral,secondary symptom integral at the 3rd and the 5th day.Conclusion:Shixinyatong buccal tablet is effective in the preven-tion of complications after the extraction of mandibular third molar.

Formulation and Evaluation of Repaglinide Buccal Tablet: Ex Vivo Bioadhesion Study and Ex Vivo Permeability Study.

The present work was performed to develop and evaluate buccal tablet containing antidiabetic drug (Repaglinide). Ethyl cellulose was used as backing membrane and Carbopol 934p, Polyox wsr N-80 NF, HEC and HPC was used as bucco adhesive polymer. Aspartame was used as sweetener. Thickness, Hardness, weight variation and drug uniformity were investigated. The tablet formulations were also subjected to drug release in 250ml 6.8 phosphate buffer. Ex vivo bioadhesion, retention time and permeation through porcine buccal mucosa membrane. Effects of different bucco adhesive polymer were evaluated on release and bioadhesion, retention time and permeation of drugs. F5 formulations showed maximum amounts of drugs release (87.18%) at the end of 10 h dissolution study. F5 also showed maximum bioadheion (0.0754N) and the resident time of F5 formulation was 9.2 h. It shows 41.52% drug release after 10 h permeation study through porcine buccal mucosa mounted in Franz cell. The tablet also found stable in human saliva after 10hr. The tablet was not showed any type of physical changes after the completion of 10 h. The results of the study suggested that new buccal tablet formulations of combined bucco adhesive polymers can be suitably developed as an alternate to conventional dosage forms.

Effect of formulation parameters on Sumatriptan succinate Buccal Mucoadhesive Tablet: Quality by Design approach.

The present investigation was focused on application of QbD approach to see the effect of formulation variables on buccal mucoadhesive tablets containing anti migraine drug, Sumatriptan succinate to circumvent the first pass effect and to provide sustained release. Risk assessment of critical material and process parameters are linked to critical quality attributes (CQAs) of the product with respect to obtain total quality product profile (TQPP). The effect of critical parameters (polymer: drug ratio, carbopol: HPMC E5 ratio and diluent quantity) were investigated by executing design of experimentation (DoE) using Box-Behnken statistical model. DR10 hr (drug release after 10 hrs), mucoadhesive strength and mucoadhesion time were considered critical quality attributes (CQAs). Sumatriptan succinate buccal mucoadhesive (SBM) tablets were prepared by direct compression method and were evaluated as per pharmacopoeia procedure. Multiple regression analysis and ANOVA were employed to identify and estimate the effect of important parameters and establish their relationship with CQAs and to obtain design space for optimization purpose. The best in-vitro drug release profile, mucoadhesive strength, mucoadhesion time and desired product quality was achieved with the formulation prepared in the region of design space. FDS graph, 3D response graph and Overlay plot were successfully implemented to interpret effects and selection of significant parameters on CQAs. Hence, it can be concluded that formulation parameters affects the SBM tablet and can be successfully optimized using the QbD a novel approach resulting into the SBM tablets which could provide sustained effect and avoid first pass effect.

Phase Ⅱ clinical trial of Shixinyatong buccal tablets in the treatment of gastropyretic toothache(pericoronitis) / 实用口腔医学杂志

Objective: To study the effects and safety of Shixinyatong buccal tablets in the treatment of gastropyretic toothache (perico-ronitis). Methods: Randemized, double-blinded, double-imitated, parallel-controlled and multi-center clinical study was employed. 120 cases of gastropyretic toothache (pericoronitis) was enrolled in the experimental group( SBT group) and another 120 in control group(CBD group). Pericoronal pocket rinsing was performed for each case at the first visit, then the patients in SBT group were treated by Shixin buccal tablets(SBT) , 0. 6 g×2, 4/d and oral adiministration of the vehicle of cow-bezoare detoxicating tablets,0.3 g×3, 3/ d. The patients in CBD group were treated by oral adiministration of cow-bezoare detoxicating tablets ( SBD), 0. 3 g×3, 3/d and the vehicle of SBT, 0.6 g ×2, 4/d respectively. Pain, gingiva contagious tumefaction, pyorrhea of periocoronal pocket and limitation of mouth opening were scored by 0, 2, 4 and 6 as the major physical signs and symptoms(MAS); periocoronal flap and pocket, facial swelling, hot and foul breath, costipation, lymphadenectasis, thirsty and desire of cold drinks, fever by 0, 1,2 and 3 as the minor (MIS). Treatment was continued for 5 days and data were statistically analysed with SAS6. 12 software. Significant effectiveness was i-dentified by the decrease of total score of all the physical signs and symptoms(TS) ≥70% .effectiveness 30%～69% and ineffectiveness ≤29%. Routine examinations of blood, urine and stool, function of liver and kidney and electrocardiogram were conducted before and after treatment. Adverse events(AE) were observed. Results: 3 cases divorced from SBT group and 2 from CBD group. The demographic data and all the scores before treatment were not statistically different between groups (P>0.05). 3 and 5 days after treatment theTS, TSMA and TSMI were decreased(P= 0.000) in both groups, in SBT group decreased more than in CBD(P<0.001). Significant effectiveness ratio of SBT group was higher than that of CBD (P=0. 000). 5 days after treatment TS of MASs and the scores of each MAS in SBT group decreased more than in CBD( P<0.05). Vital signs were in normal range and not statisticaly different between groups(P>0.05). The clinical lab examinations showed no abnormal changes. Drug-related AE were observed in 3 cases, 1 with moderate AE in SBT group recovered after drug withdrawal, 2 with mild AE in CBD group recovered without aditional treatment. Conclusion; Shixinyatong buccal tablet is more effective in the treatment of gastropyretic toothache (pericoronitis) than cow-bezoare detoxicating tablets and with similar safety.

Study on process for Bingpeng Buccal Tablet / 中成药

Objective:To research the problems in processing Bingpeng Buccal Tablet such as texture, pressure and stability etc. Methods: The alternation of supplementary materials and adhesives affect the difference of the granule in preparing Bingpeng Buccal Tablet, also studying its humid absorption utilizing the interface relative humidity. Results: The exterior and content etc. accords with the demand ,the texture and stability are fine, the accepting product rate is 91.04%. Conclusion: The process is reasonable and favorable for industrial production.

Comparison of in vitro dissolution between Fritillaria Pill and Beixinggan Buccal Tablets / 中成药

AIM:To compare the dissolution in vitro between Beimu Pills(Bulbus fritillariae cirrhosae,Radix et Rhizoma glycyrrhizae,Semen armeniacae amarum) and Beixinggan Buccal Tablet(70% alcohol percolate of Bulbus fritillariae cirrhosae;extract of Radix et Rhizoma glycyrrhizae and extract of semen armeniacae amarum) to evaluate the reform of the traditional solid preparation.METHODS:Verticine and verticinone were adopted as the reference substance for the calculation of cumulative dissolution percentage.RESULTS:Cumulative dissolution reached 95% of dissolution rate,it took 60 min for Beixinggan Buccal Tablet and it took 180 min for Beimu Pills at the same condition.CONCLUSION:Dissolution method applied to the control over TCM preparation quality and to the reform of preparation can be recognized as one of the quality standard.

Experimental Study on Antipyretic and in Vitro and in Vivo Bacteriostatic Effects of Xuanmia-Yankang Buccal Tablets(XBT) / 中国药房

OBJECTIVE:To study the antipyretic,in vitro and in vivo bacteriostatic effects of XBT METHODS:Experimen_ts were carried out on a rat model of using dry-yeast as pyretogenic agent and by conventional in vitro and in vivo antimicrobial tests,and the antipyretic and bacteriostatic effects of XBT were observed RESULTS:XBT can significantly inhibit the pyretogenesis induced by dry-yeast in rats;The result of antimicrobial experiment showed that XBT could significantly inhibit ?-hemolytic streptococcus,?-hemolytic streptococcus,streptococcus pneumaniae,and staphylococcus aureus in vitro It showed protective effects on infection with ?-hemolytic streptococcus CONCLUSION:XBT have antipyretic and bacteriostatic effects