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145ADVANCES IN MATRIX TYPE DRUG DELIVERY SYSTEMS: A COMPREHENSIVE REVIEW
Korna Devamani
Asst. Professor, Department of Pharmaceutical Analysis, Princeton College of Pharmacy, Hyderabad, Telangana, India
Kurma Kirankumar
Asst. Professor, Department of Pharmaceutical Analysis, Princeton College of Pharmacy, Hyderabad, Telangana, India
Abstract - An effective controlled release drug delivery system can be a significant step toward resolving issues related to controlling the rate of drug delivery to the target tissue and directing a drug toward a specific organ or tissue. When developing a controlled release formulation for oral consumption, the matrix tablet is an intriguing option. The current study focuses on the various polymers used to make Matrix Tablets and oral controlled release dosage forms. In the process of making pharmaceuticals, the use of polymers to control the rate at which drugs are released has grown in importance.
Keywords: Matrices, Polymer, Therapeutic, Diffusion, Erosion, and Dissolution.
1 INTRODUCTION
Among the various routes (nasal, ophthalmic, rectal, transdermal, and parentral routes) that have been investigated for the systemic delivery of drugs through pharmaceutical products of various dosage forms, oral drug delivery is the mode of administration that is used the most frequently. Due to its ease of administration, patient acceptance, and cost-effective manufacturing process, the oral route is regarded as the most natural, straightforward, convenient, and safe [in comparison to the parenteral route]. The majority of pharmaceutical products that are intended for oral delivery are immediate release type or conventional drug delivery systems, which are intended for immediate release of the drug for rapid absorption. These prompt delivery measurement structures have a few impediments, for example: Drugs with a short half-life necessitate frequent administration, increasing the likelihood of missed doses and poor patient compliance. Because of the typical peak-valley plasma concentration-time profile, it is challenging to attain the steady state condition. The undeniable vacillations in the medication fixation might prompt under prescription or
overmedication as the CSS values fall or ascend past the restorative reach.
When overmedication occurs, the fluctuating drug levels may precipitate adverse effects, particularly when the drug has a low therapeutic index.
A number of technical advancements have resulted in the development of controlled drug delivery systems, which have the potential to revolutionize the method of medication and provide a number of therapeutic benefits, in order to overcome the shortcomings of conventional drug delivery systems.
1.1 Controlled Drug Delivery Systems Controlled drug delivery systems have been developed that are able to control the rate of drug delivery, maintain therapeutic activity for an extended period of time, or target drug delivery to a specific tissue.
1.2 Matrix Tablets
Direct compression of a mixture of drug, retardant, and additives to form a tablet in which the drug is embedded in a matrix of the retardant is one of the least complicated methods for manufacturing
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146 controlled release dosage forms.Alternately, the drug and retardant mixture can be granulated prior to compression. These controlled drug delivery systems continuously release the drug through dissolution- and diffusion- controlled mechanisms. The drug is dispersed in swellable hydrophilic substances, an insoluble matrix of rigid non-swellable hydrophobic materials, or plastic materials to control its release.
One of the simplest methods for manufacturing sustained release dosage forms is to directly compress a mixture of the drug, retardant, and additives to create a tablet in which the drug is embedded in a matrix of the retardant.
Alternately, prior to compression, the drug and retardant blend can be granulated. Both hydrophilic and hydrophobic polymers are the materials that are most frequently used in the process of making matrix systems.
Hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), hydroxyethylcellulose (HEC), Xanthan gum, sodium alginate, polyethylene oxide, and cross-linked homopolymers and copolymers of acrylic acid are examples of hydrophilic polymers that are readily available. Because a small particle size is necessary for the rapid formation of a gelatinous layer on the tablet surface, it is typically provided in micronized forms. 8- 10 The introduction of matrix tablets as sustained release (SR) has resulted in a new breakthrough for pharmaceutical technology's novel drug delivery system (NDDS). The drug release rate from the dosage form is primarily controlled by the type and proportion of polymer used in the preparations, and complex production procedures like coating and pelletization are not included in this process. A lot of times, a hydrophilic polymer matrix is used to make an SR dosage form has increased its focus on the creation of sustained release or controlled release drug delivery systems due to the
increased complexity and cost of marketing new drug entities.
2 OBJECTIVES
As of late, controlled discharge drug conveyance has turned into the norms in the advanced drug plan and serious exploration has been embraced in accomplishing much better medication item adequacy, dependability and security. The majority of drug delivery systems will continue to be administered orally via sustained release. As a result, this project focuses on developing tablets to reduce the risk of first-pass metabolism and improve bioavailability. As a result, the goal of this work was to develop a sustain release system that could produce a consistent plasma concentration profile for up to 24 hours. The selection of API as the model drug was based on its low water solubility and high permeability as a BCS class II drug. Additionally, it is required to maintain drug release.
20 percent bioavailability following oral administration are design features for sustain release tablets.
Lower dose dumping danger.
Less variation between and within subjects.
A high degree of dispersion throughout the digestive system, reducing the likelihood of elevated drug concentrations in the local area.
Due to reproducible bioavailability, the drug may reach the optimal absorption site.
Drug transport is unaffected by emptying the stomach.
2.1 Advantages of Matrix Tablet
• Versatile, efficient, and inexpensive
• Capable of releasing compounds with a high molecular weight
• The sustained release formulations may maintain therapeutic concentrations for extended periods of time
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147• The high blood concentration is avoided when sustain release formulations are used.
• The patient's compliance may rise with sustain release formulations.
• Slow down the drug's absorption to reduce its toxicity.
• Protect the drug from hydrolysis or other derivative changes in the gastrointestinal tract to improve its stability.
• Reduce the local and systemic side effects to a minimum.
3 CLASSIFICATION OF MATRIX TABLETS
3.1 On the Basis of Retardant Material Used
Matrix tablets can be divided in to types.
1. Hydrophobic Matrices (Plastic matrices)
In 1959, the idea of using materials that are hydrophobic or inert as matrix materials was first presented. In this method, the drug is combined with an inert or hydrophobic polymer before being compressed into a tablet for sustained release. The dissolving drug has diffused through a network of channels between compacted polymer particles, resulting in sustained release. Polyethylene, polyvinyl chloride, ethyl cellulose, and acrylate polymers and their copolymers are examples of materials that have been utilized as inert or hydrophobic matrices.
In these formulations, liquid penetration into the matrix is the rate-controlling step. Diffusion is one possible method by which such tablets could release drugs.
Such kinds of framework tablets become dormant within the sight of water and gastrointestinal liquid.
2. Lipid Matrices
These prepared matrices made from materials related to lipid waxes Drug discharge from such networks happens through both pore dispersion and disintegration. As a result, digestive fluid composition has a greater impact on release characteristics than does an
entirely insoluble polymer matrix.
Carnauba wax in mix with stearyl liquor or stearic corrosive has been used for retardant base for some supported delivery plan.
3. Hydrophilic Matrices
The cost-effectiveness, flexibility, and widespread regulatory acceptance of hydrophilic polymer matrix systems make them a popular choice for oral controlled drug delivery. In the field of controlled release, hydrophilic polymers with high gelling capacities serve as base excipients for drug formulation in gelatinous capsules or, more frequently, tablets. A well-mixed composite of one or more drugs and a gelling agent (hydrophilic polymer) is known as an "infect a matrix."
3.2 On the Basis of Porosity of Matrix Additionally, matrix systems can be categorized as macro porous based on their porosity; Systems with and without pores can be distinguished:
1. Macro Porous Systems: The drug diffuses in these systems through matrix pores that range in size from 0.1 to 1 m.
The diffusant molecule's size is smaller than this pore size.
2. Micro Porous System: Dissemination in this sort of framework happens basically through pores. Pore sizes in microporous systems range from 50 to 200 A°, which is about the same size as diffusant molecules.
3. Non-porous System: Non-permeable frameworks have no pores and the atoms diffuse through the organization networks. There is only the polymeric phase and no pore phase in this instance.
3.3 Physicochemical Factors Influencing Release from Matrix Tablet Dose size
The bulk size of the dose that can be administered is limited for systems that are administered orally. For a conventional dosage form, a single dose of 0.5-1.0 g is typically considered maximal.
This is also true for the sustained release
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148 form. Sometimes, compounds that needto be given in large doses can be given in multiple doses or made into liquid systems. The margin of safety involved in administering a large quantity of a drug with a restricted therapeutic range is another consideration.
3.4 Ionization, Pka and Aqueous Solubility
The majority of drugs are just acids or bases. It is essential to keep an eye on the connection between the compound's pka and the absorptive environment because the unchanged form of a drug preferentially penetrates lipid membranes.
It is beneficial for drug penetration to present the drug unchanged. Sadly, the fact that the drug's aqueous solubility will typically decrease upon conversion to its unchanged form complicates the situation further. Diffusion or dissolution-based delivery systems will also be dependent on the drug's solubility in aqueous media.
These measurements structures should work in a climate of evolving pH, the stomach being acidic and the small digestive system more nonpartisan, the impact of Telephone the delivery cycle should be characterized. Compounds with extremely low solvency (<0.01mg/ml) are intrinsically maintained, since their delivery throughout the time course of a dose structure in the GI parcel will be restricted by disintegration of the medication. Because the driving force for diffusion, which is the drug's concentration in solution, will be low, it is evident that the solubility of the compound will not be a good choice for drugs that are only slightly soluble.
3.5 Partition Coefficient
At the point when a medication is managed to the GI plot, it should cross various natural layers to deliver a remedial result in one more region of the body. These membranes are frequently thought to be lipidic; As a result, the efficiency with which oil-soluble drugs
penetrate the membrane barrier depends on their partition coefficient. Compounds with a high partition coefficient that are lipophilic in nature are poorly soluble in water and remain longer in lipophilic tissue. Compounds with a low partition coefficient have a hard time getting through the membrane, which makes them less bioavailable. Furthermore, diffusion through polymer membranes is subject to the same partitioning effects.
The drug's partitioning properties must heavily influence the choice of diffusion- limiting membranes.
3.6 Stability
Orally regulated medications can be dependent upon both corrosive base hydrolysis and enzymatic corruption.
Drugs in their solid state will degrade at a slower rate; Consequently, this is the preferred delivery format for problem cases. Systems that extend delivery throughout the entire course of transit in the gastrointestinal tract are advantageous for dosage forms that are unstable in the stomach; This is also true for systems that wait for the dosage form to reach the small intestine before releasing it. When given in a sustained dosage form, compounds that are unstable in the small intestine may exhibit decreased bioavailability. This is due to the fact that more drugs pass through the small intestine and are subject to degradation there. Examples of such drugs include probanthine and propentheline.
4 CONCLUSION
Based on the above discussion, it is easy to draw the conclusion that sustained- release formulations improve patient compatibility while also increasing dose efficiency. Additionally, each of these is reasonably priced. When it comes to antibiotics, where irrational use may result in resistance, the dosage form is very helpful and simple to optimize.
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149 REFERENCES1. Chalo CSL, Robinson JR, Lee VHL. Sustained Release Drug Delivery Systems. Remington’s Pharmaceutical Sciences. 17th ed. Mack;
1995.
2. Brahmankar DM, Jaiswal SB.
Biopharmaceutics and Pharmacokinetics a Treatise. 1st ed. New Delhi: Vallabh Prakashan; 1995.
3. Chein YW. Noval Drug Delivery Systems. 2nd ed., New York: Marcel Dekker; 1992:1-42.
4. Jain NK. Pharmaceutical Product Development. 1st ed., New Delhi: CBS Publishers and Distributors; 2006, 419-424.
5. Modi SA, Gaikwad PD, Bankar VH, Pawar SP.
Sustained Release Drug Delivery System: A Review, Int J Pharma. Res Dev 2011, 2(12), 147-160.
6. Loyd V. Allen. Jr, Nicholas G. Popvich, Howard C. Ansel. Ansel’s Pharmaceutical dosage forms and drug delivery system, 8th edition, 260-263.
7. Yie. Novel Drug Delivery System, Yie W.chein, 1992, 139-150.
8. Remington, the Science and practice of pharmacy, Lippincott Williams & Wilkins 20th edition, 2002, 903-914.
9. ME Aulton, “Pharmaceutics” The Science of dosage form design, Churchill Livingstone, 2nd edition, 2002.
10. Joshep R Robinson, Vincet H Lee. Controlled drug delivery, Marcel Dekker, 2nd edition, 1987, 4-15.
11. Altaf AS, Friend DR, MASRx and COSRx Sustained-Release Technology in Rathbone MJ, Hadgraft J, Robert MS, Modified Release Drug Delivery Technology, Marcell Dekker Inc., New York, 2003.
12. Vidyadhara S, Rao PR., Prasad JA. Indian J.Pharm Sci, 2004, 66, 188-192.
13. Reddy KR., Mutalik S, Reddy S. AAPS Pharm.
Sci. Tech., 2003, 4, 1-9.
14. Mohammed AD, James LF, Michael HR., John EH., Rajabi-Siahboomi AR. Release of propranolol hydrochloride from matrix tablets containing sodium carboxy methylcellulose and Hydroxypropyl methyl cellulose. Phar.
Dev. Tech., 1999, 4, 313-324.
15. Lee BJ, Ryu SG, Cui JH, Drug Dev. Ind.
Pharm., 1999, 25, 493-501.
16. Gwen MJ, Joseph RR, In Banker GS and Rhodes CT, Eds., Modern Pharmaceutics, 3rd Edn, Vol. 72, Marcel Dekker Inc. New York, 1996, 575.
17. Salsa T, Veiga F, Pina ME, Drug Develop. Ind.
Pharm., 1997, 23, 931.
18. Jantzen GM, Robinson JR, Sustained and controlled-release drug delivery systems, in Banker GS, Rhodes CT (Eds.) Modern Pharmaceutics, Third Edition, Revised and Expanded, Drugs and the Pharmaceutical Sciences, vol 72, Marcell Dekker, Inc. New York, 1995, 575-609.
19. Bechgaard H, Nielson GH. Controlled release multiple units and single unit dosage; Drug Dev. & Ind. Pharm., 1978, 4(1), 53-67.
20. Alford N Martin, Patrick J. Sinko. Martin’s Physical pharmacy and pharmaceutical sciences, 2006.
21. Lachman L, Lieberman HA, Kanig JL. The theory and practice of Industrial pharmacy, Verghesh publishing house, 3rd edition, 1990, 346.
22. Sayed I. Abdel-Rahman, Gamal MM, El-Badry M, Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets, Saudi Pharmaceutical Journal, 2009, 17, 283-288.
23. Chandran S, Laila FA, Mantha N, Design and evaluation of Ethyl Cellulose Based Matrix Tablets of Ibuprofen with pH Modulated Release Kinetics, Indian Journal of Pharmaceutical Sciences, September-October 2008.
24. Gothi GD, Parinh BN, Patel TD, Prajapati ST, Patel DM, Patel CN, Journal of Global Pharma Technology, 2010, 2(2), 69-74.
25. Basak SC, Reddy JBM, Lucas Mani KP.
Indian Journal of Pharmaceutical Sciences, September-October 2006.
26. Varshosaz J, Tavakoli N and Kheirolahi. AAPS PharmSciTech, 2006, 7(1).
27. Raghvengra Rao NG, Gandhi S, Patel T.
International Journal of Pharmacy and Pharmaceutical Sciences, 2009, 1(1).
28. Shivhare UD, Adhao ND, Dr. Bhusari KP, Dr.
Mathur VB, Ambulkar UD. International Journal of Pharmacy and Pharmaceutical Sciences, 2009, 1(2).
29. Vyas SP, Khar RK. Controlled Drug Delivery:
Concepts and Advances. Ist ed. vallabh prakashan, 2002, 156-189.
30. Borguist P, Korner A, Larsson A. A model for the drug release from a polymeric matrix tablets-effect of swelling and dissolution, J Controlled Release 2006, 113, 216-225.
31. Nishihata T, Tahara K, Yamamoto K. Overall mechanisms behind matrix sustained release (SR) tablets prepared with hydroxypropyl cellulose 2910, J Controlled Release, 1995, 35, 59-66.
32. Siepmann J, Peppas NA, HPMC matrices for controlled drug delivery: new model combining diffusion, swelling and dissolution mechanisms and predicting the release 33. kinetics, Pharm Research 2000, 16, 1748-
1756.
34. Brahmankar HA, Jaiswal SB, Biopharmaceutics and Pharmacokinetics A Treatise, Vallabh Prakashan, 2000, 348-357 and 337.
35. Wani MS, Controlled Release System- A
Review, 2008, 6 (1),
www.pharmainfo.net/review
36. Shargel L, Yu ABC. Modified release drug products. In: Applied Biopharmaceutics and
=
VOLUME: 08, Issue 04, Paper id-IJIERM-VIII-IV, August 2021
150 Pharmacokinetics. 4th ed. McGraw Hill.1999, 169-171
37. ICH Guideline on Stability study; 2005.
38. Nandita GD, Sudip KD. Controlled-release of oral dosage forms, Formulation, Fill and Finish 2003, 10-16.
