|Year : 2015 | Volume
| Issue : 2 | Page : 82-85
Clinical evaluation of transmucosal mucoadhesive meloxicam patch in dental pain reduction: A preliminary study
Rajeshwari G Annigeri1, Manisha Jadhav1, Thimmasetty Juturu2
1 Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere, Karnataka, India
2 Department of Pharmaceutics, Bapuji Pharmacy College, Davangere, Karnataka, India
|Date of Web Publication||15-Apr-2015|
Dr. Manisha Jadhav
Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere, Karnataka
Source of Support: None, Conflict of Interest: None
Objective: To evaluate the efficacy of Meloxicam mucoadhesive patches in dental pain reduction. Study Design: It was a hospital-based study. Fifty-five patients of either sex diagnosed with dental pain were included in the study. Meloxicam patches were applied on the area of chief complaint about half an hour and pain scores were recorded. Statistical analysis was done using repeated measure ANOVA (Parametric test) with P ≤ 0.05. Result: There was a significant drop in the pain scores from baseline to the score recorded after 30 min. The pain reduction was noted to be maximum in the first 20 min. Conclusion: The result of the present study revealed significant decrease in dental pain using mucoadhesive patches with no side effects and suggests that meloxicam administered in this mucoadhesive patch may present a potential therapeutic use as a strong anti-inflammatory and analgesic agent giving further scope to carry out studies for noninvasive faster pain relief.
Keywords: Dental pain, meloxicam, mucoadhesive patches
|How to cite this article:|
Annigeri RG, Jadhav M, Juturu T. Clinical evaluation of transmucosal mucoadhesive meloxicam patch in dental pain reduction: A preliminary study. Indian J Pain 2015;29:82-5
|How to cite this URL:|
Annigeri RG, Jadhav M, Juturu T. Clinical evaluation of transmucosal mucoadhesive meloxicam patch in dental pain reduction: A preliminary study. Indian J Pain [serial online] 2015 [cited 2020 Nov 27];29:82-5. Available from: https://www.indianjpain.org/text.asp?2015/29/2/82/155174
| Introduction|| |
Pain is the most common complaint of the patient that brings him to the dentist, often occurring in conjunction with inflammation and which considerably reduce patient quality of life. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents. With the changing trends in day to day practice considerable attention has been focused in recent years on the delivery of drugs through the oral mucosa which have a disadvantage of high first pass metabolism or degrade in the gastrointestinal tract (GIT).  Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug in the body fluids, and allowing targeting and localization of a drug at a specific site. 
In oral transmucosal drug delivery, drugs are directly exposed to the oral (buccal, gingival and sublingual) mucosa and permeate across the mucosal tissues to reach the systemic circulation. There are many reports on the buccal drug delivery because it offers many advantages over peroral delivery including abundant blood supply, robustness of the epithelium, facile removal of the dosage form in case of need, satisfactory patient compliance and improved bioavailability due to avoidance of degradation in the GIT and hepatic first-pass metabolism.  However, most drugs in the term of buccal or sublingual tablets have exhibited low bioavailabilities due to the low mucosal membrane permeability and relatively small surface area available for absorption. Buccal patches are highly flexible and thus much more readily tolerated by the patients than tablets. Patches also ensure more accurate dosing of the drug compared to gels and ointments. 
Meloxicam is a NSAID belonging to the class of oxicams. It is indicated for the management of dental pain, posttraumatic and postoperative pain, inflammation and swelling. Buccal drug delivery has been considered as an interesting alternative to solve many of the problems associated with oral administration. Meloxicam possesses appropriate physicochemical properties for potential buccal delivery. It is highly potent, and the oral dose (7.5-15 mg/d) of meloxicam is the lowest of any of the NSAIDs. It has a low molecular weight (354.1), low polarity and low daily therapeutic dose.  Moreover, it has been reported that meloxicam formulations exhibit good local tissue tolerability (e.g. Occular, rectal and dermal) (Patel et al., 2011) thus, they appear to be suitable for transmucosal (such as buccal) administration. Solid dispersion loaded systems such as tablets (Hirlekar et al., 2009), creams (Madhusudhan et al., 1999), gels (Saleem et al., 2010), suppositories (Gowthamarajan et al., 2002), suspensions (Ubaidulla et al., 2005), etc showed highest drug-releasing property and increase in pharmacological activity of many poorly soluble drugs as compared to plain drug loaded systems. Therefore, in this study, an attempt was made to develop solid dispersion loaded buccal patches of meloxicam to provide ease of administration and eliminate GI side effects of meloxicam by releasing the drug completely and directly into the bloodstream of the patient.
Hence, this study aims at assessing the efficacy of meloxicam mucoadhesive patches in dental pain reduction.
| Materials and Methods|| |
The study was conducted on subjects attending the outpatient Department of Oral Medicine and Radiology, College of Dental Sciences, Davangere, Karnataka, India; after obtaining an informed consent from the patients. Ethical clearance was obtained from the Institutional Review Board, College of Dental Sciences Davangere. Fifty-five patients diagnosed with dental pain were included in the study. Inclusion Criteria were patients clinically diagnosed with dental pain; patient had not taken any analgesic 1 day before the trial and mentally sound enough to answer the visual analog scale (VAS) score. Patients allergic to meloxicam or other NSAIDs, a pregnant patient and other systemic conditions like asthma, renal impairment where the drug is contraindicated were excluded.
| Test Material|| |
Meloxicam patches were prepared in Bapuji Pharmacy College Davangere under the eminent guidance of Head of Pharmaceutical Department. The contents of the patch included: Meloxicam Drug-8 mg, polymers - hydroxyl polymethyl cellulose (HPMC) 350 mg and ethyl cellulose (EC)-50 mg, solvent - Acetone 10 ml and plasticizer dibutylphthalate eight drops. Meloxicam was solubilized in 5 ml of acetone. HPMC was solubilized in 3 ml and EC in 2 ml of acetone respectively. The polymer solutions were mixed, and eight drops of plasticizer were added. This solution was finally mixed with a solution of Meloxicam drug and was stirred on a magnetic stirrer and then poured in the molds without incorporating air bubbles. The patches were procured after 24 h of pouring and packed in aluminum foils. Mucoadhesive patches were prepared using HPMC and analyzed for quality control tests. 
| Clinical Evaluation|| |
The patients were explained about the procedure and the VAS scores (0-10). A proforma was prepared for the study where in the chief complaint, VAS scores every 5 min for 30 min and the side effects if any after 24 h through telephonic conversation were recorded.
Before receiving the patch, the patients were asked to rinse the mouth thoroughly with water to remove any food debris. The area was then mopped with cotton but not desiccated and mucoadhesive meloxicam patch of size 1 × 1 cm 2 was placed over the attached gingiva and alveolar mucosa of the area diagnosed with pain after retraction of the labial or the buccal mucosa [Picture 1]. The patch was allowed to get wet with saliva and then slowly without disturbing the patch the retracted buccal or the labial mucosa was repositioned. The patient was instructed not to talk, spit or disturb the area for half an hour. Every 5 min the VAS score was recorded. The patient was asked to mark on the proforma the VAS score with the pen. At the end of half an hour, the patch was removed and discarded. The patient was followed for 1 day by telephonic conversation to know any side effects and the duration of time for which the patient was pain free before the next analgesic dosage.
| Results|| |
The study population consisted of 30 males and 25 females. The cases consisted of acute apical periodontitis, acute periapical abscess, chronic periapical abscess and other pain of odontogenic origin. Pain due to ulcerated lesion or other carcinomatous conditions were excluded. The baseline VAS scores ranged from 2.5 to 10 with a mean of 7.29 [Graph 1] and SD 2.34. It was also ensured that subjects were not under the influence of any analgesics at the time of study. Statistical analysis was done using SPSS (version 17.0). Tests applied were repeated measure ANOVA (Parametric test) with P ≤ 0.05. Descriptive analysis was done to calculate the mean.
In terms of clinical efficacy, five individuals reported that 100% pain relief at the end of the 30 min time period, and 37 showed >50% pain reduction. The maximal pain reduction was seen in the first 20 min. The mean VAS scores recorded at baseline was 7.29 which dropped down to 3.2 at the end of the 30 min (Graph 1). There was about more than 50% pain reductions at the end of 30 min. Also one patient showed no relief in the pain score till the end of 30 min time period. The difference observed in VAS score between all the time intervals was found to be statistically significant (P ≤ 0.05) [Figure 1].
|Figure 1: The difference observed in visual analogue scale score between all-time intervals was found to be statistically significant (P ≤ 0.05)|
Click here to view
Rapid effective analgesia was achieved with the patch in almost all the patients except one where the VAS scores remained constant till the end of 30 min. In individual cases, marked analgesia was obtained where the pain was localized and spontaneous. On telephonic conversation, a maximal of 4-5 h of analgesic effect was noted before the patient had taken next analgesic.
All patients evaluated the taste and texture of the patch and pain relief. The analgesic effect was seen right from the first 5 min. Slipping of the patch was seen in five patients that was noted in the first 10 min and was replaced back. The symptoms were relieved, and no adverse effects or complaints were noted regarding the patch application.
| Discussion|| |
Nowadays the most prescribed drugs are painkillers. It has been reported that in Britain alone more than 62 million prescriptions are written by doctors every year. Despite tremendous advances in drug delivery, an oral route remains the preferred route for the administration of therapeutic agents due to low cost, ease of administration and high level of patient compliance. However, significant barriers impose for the peroral administration of drugs, such as hepatic first pass metabolism and enzymatic degradation within GI tract. Parentral route of drug delivery has got has its own snags. In recent years, there has been tremendous interest and development in the field of transmucosal delivery systems.
Gastritis is one of the most common problems faced with the most prescribed NSAIDs, and this could be circumvented with this new drug delivery system. The patch prepared was soft and very thin, which caused least discomfort to the patient during application or during the course of the treatment period. There was a significant decrease in the pain intensity within the first 5 min. The maximum pain decline was seen in the first 20 min after which the decline was gradual. The difference observed in VAS score between all the time intervals was found to be statistically significant (P ≤ 0.05). The result of the present study reveals a significant decrease in dental pain with no side effects, which is comparable with the clinical study wherein significant postoperative pain reduction was found with Lornoxicam buccal patches. 
The results of the present study were in accordance with another study wherein mucoadhesive indomethacin patches used showed rapid and effective analgesic effect in 65 patients diagnosed with various oral conditions associated with pain.  In our study, the patient had the analgesic effect for about 4-5 h before next dosage of analgesic was taken which is in accordance with a study wherein dibucaine film maintained analgesic effect for <5.5 h. 
Though the study had few shortcomings like we could not count the amount of drug percolated in 30 min which had the analgesic effect, different patients have different pain perceptions and that could have influenced the results too. This research opens a new panorama in the field of simple and faster pain relief and scope for further research.
| References|| |
Insel PA. Analgesic-antipyretic and antiinflammatory agents. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9 th
edn McGraw-Hill; New York: 1996. p. 637.
Jafar M, Ali S. Development and evaluation of meloxicam solid dispersion loaded buccal patches. J Appl Pharm Sci 2011;1:77-82.
Semalty A, Bhojwani M, Bhatt GK, Gupta GD, Shrivastav AK. Design and evaluation of mucoadhesive buccal films of diltiazem hydrochloride. Indian J Pharm Sci. 2005;67:548-52.
Thimmasetty J, Pandey G, Babu P. Design and in vivo
evaluation of carvedilol buccal mucoadhesive patches. Pak J Pharm Sci 2008;21:241-8.
Habib F, Shaltout SE, Azeem MA, Feith G, Safwat M. Mucoadhesive buccal patches of lornoxicam: In vivo
evaluation and clinical efficacy. Bull Pharm Sci 2011;34:21-30.
Kazuyo Takeuchi, Machiko Watanabe, Mashiho yanagi,Isao Murakami,Hiroyuki Hosono,Satoru Nishizawa et al. In vitro and clinical evaluation of an oralmucosal adhesive film containing indomethacin. Pharm Soc Jap 2008;128:1791-5
Yamamura M, Saijo K, Noda M, Kikuta S, Itaya K. J Jpn Hosp Pharm Assoc 1986;30:1-6.