View Article

  • Formulation And Evaluation Of Buccoadhesive Drug Delivery System Containing A Broad Spectrum Antibiotic
  • 1Department of Pharmaceutics, Laddhad college of Pharmacy yelgaon, buldhana.
    2Professor, Department of Pharmaceutics, Vidyaniketan college of Pharmacy,Amravati.
    3,4 Department of P’Quality Assurance, Laddhad college of Pharmacy yelgaon buldhana.
     

Abstract

In the present work an attempt is being made to provide for stable drug delivery system with or having improved therapeutic index for broad spectrum Macrolide antibiotic in the form of Erythromycin drug. buccoadhesive drug delivery system loaded by Macrolide antibiotic drug erythromycin as model drug for targeted delivery. Drug release studies were made to determine whether the release of is enough i.e which polymer ratio is enough to control the release of the drug for 12hr’s. Tablet of Batch F9 96.24% provided controlled release of Erythromycin over the period of 12hr’s. Respectively. In conclusion the formulation was optimized the prepared buccoadhesive tablet good reproducibility and to control release of the drug for long period of time.

Keywords

Need Of Buccoadhesive Drug Delivery System, Different approaches of buccoadhesive drug delivery, Macrolide antibiotic, Erythromycin, in vitro drug release.

Introduction

In recent years, there has been increasing interest on the use of bioadhesive polymers to control the delivery of biologically active agents systemically or locally. These bioadhesive systems are useful for the administration of drugs, which are susceptible to extensive Gastro intestinal degradation and first pass metabolism. Buccal bioadhesive system appears to be attractive because it avoids significant limitations of traditional routes and first pass metabolism. Buccal delivery necessitates the use of mucoadhesive polymer as these dosage forms should ideally adhere to the mucosa and withstand salivation, tongue movement and swallowing for a significant period of time1. Traditionally, per-oral delivery has been the primary route of administration for therapeutic agents targeting systemic delivery. Technologic advances in biomaterials and techniques have resulted in the formulation of novel designs more pertinent to the oral cavity, meeting the challenges of the physicochemical properties of the drug entity itself and achieving the therapeutic aims of the drug delivery system. Issues of patient compliance and convenience have recently resulted in a trend toward once-a-day administration regimens, requiring drugs with high potency and sustained effect. Such drugs usually have a short biologic half-life, exhibit poor permeability and solubility, and are susceptible to enzymatic degradation. However, because of the advantages of delivering a drug through the oral mucosa, these drugs are viable candidates for delivery via this route. Many investigators have studied the potential of transmucosal delivery through the oral cavity, and the oral mucosa is increasingly being considered as an effective route for many drug classes2. A bio adhesive system plays a major role, due to its potential. Besides acting as platforms for sustained release dosage forms, bioadhesive polymers can themselves exert some control over the rate and amount of drug release and thus contribute to the therapeutic efficacy of bioadhesive drug delivery systems. Bio adhesion is an interfacial phenomenon in which two materials, at least one of which is biological, are held together by means of interfacial forces. The attachment could be between an artificial material and biological substrate, such as the adhesion between polymer and /or copolymer and a biological membrane. In the case of polymer attached to the mucin layer of mucosal tissue, the term “mucoadhesion” is employed3.Administration of the drug via the mucosal layer is a novel method that can render treatment more effective and safer, not only for the tropical diseases but also for systemic ones. These unique dosage forms, which can be applied on a thick gel-like structure known as mucin, therefore all bio-adhesives must interact with the mucin layer during the process of attachment, these represent the potential sites for attachment of any bioadhesive system wet tissue, are formulated by utilizing the adhesive properties of some water – soluble polymers. The mucosal layer lines a number of regions of the body including the gastrointestinal tract, buccal cavity, airways, ear, nose, eye, urogenital tract, vagina and rectum are covered4. Transmucosal routes of drug delivery involve the delivery of the drug through the mucosal linings of the nasal, rectal, vaginal, ocular, and oral cavity. Amongst these oral cavities is a novel site for drug delivery. The oral mucosa has been investigated in several studies as a means to give both local and systemic amounts of drug. Drug delivery across the oral mucosa, can be divided into three different types5,6.

1. Sublingual delivery, consisting of administration through the membrane of the ventra surface of the tongue and the floor of the mouth.

2. Buccal delivery, consisting of administration through the buccal mucosa, mainly composed of the lining of the cheeks.

3. Local delivery, consisting of administration through all areas other than former two regions. These sites differ anatomically in their permeability to drugs, rate of drug delivery, and ability to maintain a delivery system for the time required for drug release out of the delivery apparatus and into the mucosa7.

Different approaches of Bucco adhesive drug delivery8:

  1. Buccal drug delivery system.
  2. Sublingual drug delivery system.
  3. Rectal drug delivery system.
  4. Nasal drug delivery system.
  5. Vaginal drug delivery system.
  6. Occular drug delivery system.
  7. Gastrointestinal drug delivery system.

Need Of Bucco adhesive Drug Delivery System9:

  1. Control release.
  2. Target and localized drug delivery.
  3. By pass first pass metabolism.
  4. Avoidance of drug degradation.
  5. Prolonged effect.
  6. High drug flux through absorbing tissues.
  7. Reduction in fluctuation in steady state plasma level.

Buccal mucoadhesive drug delivery system10-13:

Advantages of buccal mucoadhesive drug delivery system:

  1. Buccal mucosa has rich blood supply due to it’s high vascularization and so the drug easily absorbed through it.
  2. Prolongs the residence time of the dosage form at the site of absorption.
  3. Faster onset of action is achive due to the mucosal surface.
  4. The drug gain direct entry into the systemic circulation thereby bypassing the first pass effect.
  5. Avoidance of presystemic elimination within the gastrointestinal tract.
  6. Good accesability and it has better patient complience due to the elimination of associated pain with injection.
  7. Large contact of the sarface of the oral cavity contributes to rapid and extensive drug absorption.
  8. Nausea and vomitting are greatly avoided.

Disadvantages of buccal mucoadhesive drug delivery system:

  1. Drugs which are unstable at buccal pH cannot be administered.
  2. Drugs which irritate the mucosa or have a bitter or unpleasant taste or an obnoxious odour cannot be administered by this route.
  3. Only drug with small dose requirement can be administered.
  4. Only those drugs which are absorbed by passive diffusion can be administered by this route.
  5. Eating and drinking may become restricted.

Materials

Erythromycin was obtained from Alkem Pvt Mumbai, other chemicals and reagent used were of analytical grade.

METHODOLOGY

Preparation of Bucco adhesive Tablet

Erythromycin, HPMC K4M, HPMC K15M, HPMC 100M , Carbopol 974P  and Mannitol were blended homogeneously in mortar as the quantity given in table. Blended mixture was passed through the 60No. Sieve and magnesium stearate 1% was added and blended. The homogeneously blended mixture was compressed in rotary tablet press with the flat punch.

       
            composition of Bucco adhesive Erythromycin Tablet..png
       

Table- 1: composition of Bucco adhesive Erythromycin Tablet.

 

Evaluation of Tablet

Formulated tablet was evaluated for the different parameter for evaluation. Following parameter used for the evaluation of formulation.

Weight variation test

Twenty tablets were weighed individually and the average weight was calculated. the individual weight were then compared with the average weight. The tablet pass the test if not more than two tablets fall outside the percentage limit and none of the tablets differ by more than double the percentage limit given below.

       
            Weight variation limit14.png
       

Table- 2 Weight variation limit14

 

Drug Content Uniformity

Twenty Tablets were weighed and crushed to obtain a fine powder. An accurately weighed sample equivalent to 100 mg of Erythromycin was taken in a stoppered volumetric flask (100ml); 50ml of acidic buffer pH 6.8 was added. The solution was filtered paper (No 41) and the volume was made up to the mark with the same solvent. the aliquot portion of above solution were further diluted with phosphate buffer of pH 6.8 get final concentration about 100µg/ml Erythromycin and absorbance were measured at 285 nm against blank. The concentration of drug in sample were calculated15.

Hardness and Friability

The Monsanto hardness tester was used to determine the tablet hardness. The tablet was held between a fixed and moving jaw, the body of Monsanto hardness tester carries an adjustable scale which was set a zero against an index mark fixed to the compression plunge. When the table was held between the jaws. The load was gradually increased until the tablet fractured. the value of the load at the point gave a measure of the tablet hardness.  Friability was evaluated by means of friability test apparatus known as Roche friabilator and then operated at 25rpm for 4 minutes. The tablets were then removed and weighed again. The difference in the two weight was used to calculate friability.16

F= 100×[1-W/W0]

Where Wo- Initial weight

W- Final weight

Thickness The thickness of tablet was measured by vernier calliper.17

Bio adhesion Strength and Bio adhesion Time18

Bio adhesive strength of the buccal tablets was measured on the “Modified Physical Balance method”. The method used goat buccal membrane as the model mucosal Balance method.” The fresh goat buccal mucosa was cut into pieces and washed with phosphate buffer pH 6.8 A piece of mucosa was tied to the glass slide which was moistened with phosphate buffer 6.8. the tablet was stuck to the lower side of another glass slide with glue. The both pans were balanced b adding an appropriate support, so that the tablet touches the mucosa. On the side of balance powder (equivalent to weight) was added slowly to it until the tablet detach from the mucosal surface gave the bio adhesive strength. The experiment was performed in triplicate and average value was calculated. Bio adhesive strength which was measured as force of adhesion in Newton by using formula.

Force of adhesion (N) = Mucoadhesive strength / 100×9.81

Bio adhesion Time Determination

The ex-vivo mucoadhesion time was examined after application of the buccal tablet on freshly cut goat buccal mucosa. The fresh goat buccal mucosa was tied on the glass slide, and a mucoadhesive core side of each tablet was wetted with 1 drop of phosphate buffer pH 6.8 and pasted to the sheep buccal mucosa by applying a light force with a fingertip for 30 second. The glass slide was then put in the beaker, which was filled with 200ml of the phosphate buffer pH 6.8 and kept at 37±10c. After 2 minutes, stirring was applied slowly to stimulate the buccal cavity environment, and tablet adhesion was monitored for 8hr. The time for the tablet to detach from the goat buccal mucosa was recorded as the mucoadhesion time.

In vitro dissolution study15

In- vitro release study of tablet was done by using USPXXII dissolution test apparatus. Jar was filled with Phosphate buffer pH 6.8 and temperature was maintained at 37±0.5 0c. Paddle was revolved at 100 rpm speed. Five ml of sample was withdrawn after interval of 1 hour and replaced with 5 ml fresh dissolution medium to maintain sink condition. sample were then analysed spectrophotometrically for drug content at 285 nm.

       
            In vitro dissolution study..png
       

Table No- 3: In vitro dissolution study.

 

RESULTS AND DISCUSSION

Evaluation of optimized formulation

All the formulation were evaluated for the parameter such as drug content, friability and hardness, Weight Variation, Thickness

       
            Post compression properties of formulation.png
       

Table- 4: Post compression properties of formulation

 

All the formulation evaluated for the important parameter; result obtained were shown in   table. The average weight from all the formulation were found be in the range 424 - 466, indicates that all the batches have the average weight as per official standards. The drug content in all the batches in the range of 92.75 - 99.24 %. All the batches have good hardness and friability as per standards.

Bio adhesive strength and bio adhesive time of formulation:

Our ultimate aim is to formulate tablet that can adhere to membrane for about 12 hours and release the drug for 12 hours. It was found that near about all formulation achieve adhesion property. It was found that there was no much difference in adhesion time of formulation.

       
            Measurement of Bio adhesive force.png
       

Table- 5: Measurement of Bio adhesive force

 

The bio adhesive property of tablet of Erythromycin containing varying proportion of polymer was determined with an insight to develop the tablet with adequate polymers was determined with an insight to develop the tablet with adequate bio adhesiveness.  For the maximum adhesion of tablet with in buccal cavity the tablet should possess the some bio adhesive strength was found to be in range of 11.31 – 41.43 The highest adhesion force and highest strength of the mucoadhesive bond was observed with the formulation F8 and F12. Tablet of formulation F1and F2 containing showed least adhesion force than tablet of all others formulation. Bio adhesion time was also found to be optimum which is require for the formulation to be remain within the buccal cavity.

       
            Bio adhesive strength of different formulation.png
       

Figure- 1: Bio adhesive strength of different formulation

In Vitro drug release study

All the formulation evaluated for the percentage drug release. Following result obtained from the different formulations after 12 hr’s drug release study was carried out.

       
            Dissolution Profile of various formulation.png
       

Table-6: Dissolution Profile of various formulation

 

Drug release studies were made to determine whether the release of is enough i.e. which polymer ratio is enough to control the release of the drug for 12hr’s. Various polymer used like Hydroxy propyl methylcellulose K4M, Hydroxy propyl methylcellulose K15, Hydroxy propyl methylcellulose 100M and Carbopol 974P used as hydrophilic matrix forming and mucoadhesive polymer in varying concentration. As result of drug release study individual polymer shows that the HPMC K4M, HPMC K15M, HPMC 100M, and Carbopol 974-P alone was able to control the release in 12hr’s. Release of Erythromycin, from the combination HPMC 100M and Carbopol 974-P gave the good result compared to employing individual polymers. Tablet of Batch F9 96.24% provided controlled release of Erythromycin over the period of 12hr’s. Respectively.

       
            % Drug Release of Formulation.png
       

Figure-2: % Drug Release of Formulation

CONCLUSION

From the performed work it was concluded that, Development of Bucco adhesive buccal drug delivery of Erythromycin is one of the alternative routes of administration to avoid first pass metabolism and to achieve controlled release drug delivery. The formulation containing HPMC K100M and Carbopol 974-P Was found to be optimized batch and was prepared by direct compression method. This study suggests that the Polymer HPMC K100M And Carbopol 974-P Batch F9 can produce controlled pattern of drug release in the prepared Erythromycin tablet. The optimized batch F9 showed 96.24% drug release in 12hr. The surface pH of optimized formulation was found to be 6.7 This pH is near to the neutral therefore, the formulation does not cause any irritation on the buccal mucosa. All the physical parameter were found satisfactory. Therefore, Bucco adhesive formulation of Erythromycin may be good way to by-pass first pass metabolism.

REFERENCE

  1. Elnay JC, Swarbick J, Boylan JC. Encyclopedia of pharmaceutical technology. 2nd ed. New York: Marcel Dekkar.1990; 189.
  2. N. S. Miller, M. Chittchang, T. P. Johnston. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Delivery Review.2005; 57:1666- 91.
  3. N. K. Jain. Controlled and novel drug delivery. 1st ed. CBS Publishers, New Delhi, 2002.
  4. Chowdary KPR, Srinivas L. Mucoadhesive drug delivery systems: A review of current status. Indian drugs 2000;37(9):400-06.
  5. Khanna R, Agarwal SP, Ahuja A. Mucoadhesive buccal drug delivery: A potential alternative to conventional therapy. Indian Journal of Pharmaceutical Science 1998;60(l):111.
  6. Senel S, Kremer M, Nagy K, Squier C. Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol 2001;2:175-86.
  7. Khairnar GA, Sayyad FJ. Development of buccal drug delivery system based on mucoadhesive polymers. International Journal of PharmTech Research. 2010;2(1): 719-735
  8. SA Abnawe. Mucoadhesive drug delivery system. Pharmainfo.net. 2009.
  9. P Tangri, NVS Madhav. Recent advance in oral mucoadhesive drug delivery system: A review. IJPRD. 2011; 3: 151-162.
  10. M Alagusundaram, CM Chetty, D Dhachinamoorthi. Advances in buccoadhesive drug delivery system: A review. Int J Rev Life Sci. 2011; 1: 35-44.
  11. KV Patel, ND Patel, HD Dodiya, PK Shelat. Buccal bioadhesive drug delivery system: An overview. IJPBA. 2011; 2: 600-609.
  12. GA Khairnar, FJ sayyad. Development of buccal drug delivery system based on mucoadhesive polymers. Int J Pharm Tech Res. 2010; 2: 719-735.
  13. VV Prasanth, S Mudiyala, ST Mathew, R Mathapan. Buccal tablet-As mucoadhesive drug delivery : An overview. J Pharm Res. 2011; 3: 706-709.
  14. Indian Pharmacopoeia Published by the Controller of Publication. New Delhi, Vol. I & II;762,610;1996.
  15. Mudedla Suresh1*, Debjit Bhowmik1, Praveen Khirwadkar2, K.P.Sampath Kumar3, Rajnish Kumar Singh4  Formulation and evaluation of mucoadhesive tablet of Clarithromycin   Indian Journal of Research in Pharmacy and Biotechnology ISSN: 2321-5674
  16. Gavaskar B.et al .formulation and evaluation of mucoadhesive tablet baclofen. IJPT/ june2010/vol.2/issue no.2/396-409.
  17. Leon Lachman and Herbert A. Liberman et al. The theory and practice of Industrial Pharmacy, 3rd edition. Varghese publication,455
  18. Anup Kumar Roy1* Vinod kumar sm1 Syed Jalaluddin Basha1 Rabiul Haque 2Roopa Karki 1 Formulation and evaluation of Mucoadhesive Buccal tablets ofValsartan Int. J. Drug Dev. & Res., October -December 2013, 5 (4): 145-155

Reference

  1. Elnay JC, Swarbick J, Boylan JC. Encyclopedia of pharmaceutical technology. 2nd ed. New York: Marcel Dekkar.1990; 189.
  2. N. S. Miller, M. Chittchang, T. P. Johnston. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Delivery Review.2005; 57:1666- 91.
  3. N. K. Jain. Controlled and novel drug delivery. 1st ed. CBS Publishers, New Delhi, 2002.
  4. Chowdary KPR, Srinivas L. Mucoadhesive drug delivery systems: A review of current status. Indian drugs 2000;37(9):400-06.
  5. Khanna R, Agarwal SP, Ahuja A. Mucoadhesive buccal drug delivery: A potential alternative to conventional therapy. Indian Journal of Pharmaceutical Science 1998;60(l):111.
  6. Senel S, Kremer M, Nagy K, Squier C. Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol 2001;2:175-86.
  7. Khairnar GA, Sayyad FJ. Development of buccal drug delivery system based on mucoadhesive polymers. International Journal of PharmTech Research. 2010;2(1): 719-735
  8. SA Abnawe. Mucoadhesive drug delivery system. Pharmainfo.net. 2009.
  9. P Tangri, NVS Madhav. Recent advance in oral mucoadhesive drug delivery system: A review. IJPRD. 2011; 3: 151-162.
  10. M Alagusundaram, CM Chetty, D Dhachinamoorthi. Advances in buccoadhesive drug delivery system: A review. Int J Rev Life Sci. 2011; 1: 35-44.
  11. KV Patel, ND Patel, HD Dodiya, PK Shelat. Buccal bioadhesive drug delivery system: An overview. IJPBA. 2011; 2: 600-609.
  12. GA Khairnar, FJ sayyad. Development of buccal drug delivery system based on mucoadhesive polymers. Int J Pharm Tech Res. 2010; 2: 719-735.
  13. VV Prasanth, S Mudiyala, ST Mathew, R Mathapan. Buccal tablet-As mucoadhesive drug delivery : An overview. J Pharm Res. 2011; 3: 706-709.
  14. Indian Pharmacopoeia Published by the Controller of Publication. New Delhi, Vol. I & II;762,610;1996.
  15. Mudedla Suresh1*, Debjit Bhowmik1, Praveen Khirwadkar2, K.P.Sampath Kumar3, Rajnish Kumar Singh4  Formulation and evaluation of mucoadhesive tablet of Clarithromycin   Indian Journal of Research in Pharmacy and Biotechnology ISSN: 2321-5674
  16. Gavaskar B.et al .formulation and evaluation of mucoadhesive tablet baclofen. IJPT/ june2010/vol.2/issue no.2/396-409.
  17. Leon Lachman and Herbert A. Liberman et al. The theory and practice of Industrial Pharmacy, 3rd edition. Varghese publication,455
  18. Anup Kumar Roy1* Vinod kumar sm1 Syed Jalaluddin Basha1 Rabiul Haque 2Roopa Karki 1 Formulation and evaluation of Mucoadhesive Buccal tablets ofValsartan Int. J. Drug Dev. & Res., October -December 2013, 5 (4): 145-155

Photo
Akshay V. Patil
Corresponding author

Department of Pharmaceutics, Laddhad college of Pharmacy yelgaon, buldhana.

Photo
Dr. Gautam Mehetre
Co-author

Department of Pharmaceutics, Vidyaniketan college of Pharmacy,Amravati.

Photo
Vishal Murkute
Co-author

Department of P’Quality Assurance, Laddhad college of Pharmacy yelgaon buldhana

Photo
Preeti More
Co-author

Department of P’Quality Assurance, Laddhad college of Pharmacy yelgaon buldhana

Akshay Patil*, Dr. Gautam Mehetre, Vishal Murkute, Preeti More, Formulation And Evaluation Of Buccoadhesive Drug Delivery System Containing A Broad Spectrum Antibiotic, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 8, 2801-2808. https://doi.org/10.5281/zenodo.13286041

More related articles
Cyclodextrin Based Nanosponges: A Novel Approach F...
Kanika, Chinu Kumari, Dev Prakash Dahiya, Nikhil Rana, Rahul Shar...
Comprehensive Review on Semen Production, Prematur...
Dr. Mohd Abid, Mohd Vaseem, Abdulla Ansari, Md Furquan Khan, Naye...
An Extensive Review Study Of Solely Cloned Identic...
TIWARI POOJA, PATEL PRATIXA, MISHRA SATYAM, YADAV RUBI , ...
New Frontiers In Alcohol Withdrawal: From Mechanisms To Therapeutics...
Sunita ogale, Karishma Bhavsar, Tanvi Pingale, ...
A Review On Insights Of Professional Sales Representative And Marketing Strategi...
Sayali V. Pawar, Pratiksha N. Sapkal, Dhanaji A. Jadhav, Rutuja A. Jadhav, Mayur R. More, Rahul D. M...
Formulation And Evaluation of Floating Drug Delivery System of Benazepril...
Nagendra R., Divyashree P., Nanditha V. V., Venkatesh, K. Hanumanthachar Joshi, ...
Related Articles
Liposomes, Protein and Peptide Drug Delivery Systems...
Pratik S. Dhone, Priyanka Shelke, Gajan Sanap, ...
The Role Of Stereochemistry And Formulation In Pharmacology Of The Drug...
Mohd Sharique Katchhi, Abrar Ahmed, Disha Kumareshi, Harshitha M. V., Chakure Aditya, ...
Enhanced Oral Bioavailability Through Nanoparticle- Based Solid Lipid Carrier: A...
P.Sriramcharan , Sridevi M., Keerthana V., Vignesh S., Thabasoom E, ...
Cyclodextrin Based Nanosponges: A Novel Approach For Targeted Drug Delivery...
Kanika, Chinu Kumari, Dev Prakash Dahiya, Nikhil Rana, Rahul Sharma, Abhilash Rai, Abhishek Soni, ...
More related articles
Cyclodextrin Based Nanosponges: A Novel Approach For Targeted Drug Delivery...
Kanika, Chinu Kumari, Dev Prakash Dahiya, Nikhil Rana, Rahul Sharma, Abhilash Rai, Abhishek Soni, ...
Comprehensive Review on Semen Production, Premature Ejaculation, Contributing Fa...
Dr. Mohd Abid, Mohd Vaseem, Abdulla Ansari, Md Furquan Khan, Nayeem Ahmad, Mohd Saidurrehman, Syed S...
An Extensive Review Study Of Solely Cloned Identical Antibodies Monoclonal Antib...
TIWARI POOJA, PATEL PRATIXA, MISHRA SATYAM, YADAV RUBI , ...
Cyclodextrin Based Nanosponges: A Novel Approach For Targeted Drug Delivery...
Kanika, Chinu Kumari, Dev Prakash Dahiya, Nikhil Rana, Rahul Sharma, Abhilash Rai, Abhishek Soni, ...
Comprehensive Review on Semen Production, Premature Ejaculation, Contributing Fa...
Dr. Mohd Abid, Mohd Vaseem, Abdulla Ansari, Md Furquan Khan, Nayeem Ahmad, Mohd Saidurrehman, Syed S...
An Extensive Review Study Of Solely Cloned Identical Antibodies Monoclonal Antib...
TIWARI POOJA, PATEL PRATIXA, MISHRA SATYAM, YADAV RUBI , ...