Preparation and Evaluation of Sustained Release Calcium Alginate Beads and Matrix Tablets of Acetazolamide

Abstract

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator’s sustained-release capsule (Diamox^®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Key words

acetazolamide - alginate beads - sustained release - microencapsulation

• References

• 1 Adibkia K, Javadzadeh Y, Dastmalchi S et al. Naproxen/eudragit RS100 nanoparticles: Preparation and physicochemical characterization. Colloids Surf B Biointerfaces 2011; 83: 155-159
• 2 Javadzadeh Y, Adibkia K, Bozorgmehr Z et al. Evaluating retardation and physicochemical properties of co-ground mixture of Na- diclofenac with magnesium stearate. Powder Technol 2012; 218: 51-56
• 3 Standford ECC. New substances obtained from some of the commoner species of marinalgea. Algin, chemical News 1883; 47: 267-269
• 4 Astberg T, Graffner C. Calcium alginate matrices for oral multiple unit administration: III. Influence of calcium concentration, amount of drug added and alginate characteristics on drug release. Int J Pharm 1994; 111: 271-282
• 5 Ciofani G, Raffa V, Pizzorusso T et al. Characterization of an alginate-based drug delivery system for neurological applications. Medical Engineering & Physics 2008; 30: 848-855
• 6 Ferreira Almeida P, Almeida AJ. Cross-linked alginate/gelatine beads: a new matrix for controlled release of pindolol. J Controlled Release 2004; 97: 431-439
• 7 George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan: a review. J Controlled Release 2006; 114: 1-14
• 8 Huang X, Xiao Y, Lang M. Micelles/sodium-alginate composite gel beads: A new matrix for oral drug delivery of indomethacin. Carbohydr Polym 2012; 87: 790-798
• 9 Moebus K, Siepmann J, Bodmeier R. Alginate/poloxamer microparticles for controlled drug delivery to mucosal tissue. Eur J Pharm Biopharm 2009; 72: 42-53
• 10 Choi BY, Park HJ, Hwang SJ et al. Preparation of alginate beads for floating drug delivery system: effects of CO2 gas-forming agents. Int J Pharm 2002; 239: 81-91
• 11 Ishak RAH, Awad GAS, Mortada ND et al. Preparation, in vitro and in vivo evaluation of stomach-specific metronidazole-loaded alginate beads as local anti-Helicobacter pylori therapy. J Controlled Release 2007; 119: 207-214
• 12 Kim C-K, Lee E-J. The controlled release of blue dextran from alginate beads. Int J Pharm 1992; 79: 11-19
• 13 Xing L, Dawei C, Liping X et al. Oral colon-specific drug delivery for bee venom peptide: development of a coated calcium alginate gel beads-entrapped liposome. J Controlled Release 2003; 93: 293-300
• 14 Xu Y, Zhan C, Fan L et al. Preparation of dual crosslinked alginate/chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system. Int J Pharm 2007; 336: 329-337
• 15 Nochos A, Douroumis D, Bouropoulos N. In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohydr Polym 2008; 74: 451-457
• 16 Chickering Iii DE, Jacob JS, Desai TA et al. Bioadhesive microspheres: III. An in vivo transit and bioavailability study of drug-loaded alginate and poly (fumaric-co-sebacic anhydride) microspheres. J Controlled Release 1997; 48: 35-46
• 17 Furtado S, Abramson D, Burrill R et al. Oral delivery of insulin loaded poly (fumaric-co-sebacic) anhydride microspheres. Int J Pharm 2008; 347: 149-155
• 18 Guilherme MR, Toledo EA, Rubira AF et al. Water affinity and permeability in membranes of alginate-Ca2+ containing poly(n-isopropylacrylamide). J Membr Sci 2002; 210: 129-136
• 19 Roy A, Bajpai J, Bajpai AK. Dynamics of controlled release of chlorpyrifos from swelling and eroding biopolymeric microspheres of calcium alginate and starch. Carbohydr Polym 2009; 76: 222-231
• 20 Martins S, Sarmento B, Souto EB et al. Insulin-loaded alginate microspheres for oral delivery/Effect of polysaccharide reinforcement on physicochemical properties and release profile. Carbohydr Polym 2007; 69: 725-731
• 21 Zhang Y, Wei W, Lv P et al. Preparation and evaluation of alginate/chitosan microspheres for oral delivery of insulin. Eur J Pharm Biopharm 2011; 77: 11-19
• 22 Swenson ER. Carbonic anhydrase inhibitors and hypoxic pulmonary vasoconstriction. Respiratory Physiology & Neurobiology 2006; 151: 209-216
• 23 Buescher U, Hertwig K, Wolf C et al. Erythropoietin in amniotic fluid as a marker of chronic fetal hypoxia. International Journal of Gynecology & Obstetrics 1998; 60: 257-263
• 24 Lechermann B, Jelkmann W. Erythropoietin production in normoxic and hypoxic rats with increased blood O2 affinity. Respir Physiol 1985; 60: 1-8
• 25 Reinhart WH, Goerre S, Bartsch P. Acetazolamide reduces the erythropoietin response to hypoxia at high altitude in humans. Journal of Wilderness Medicine 1994; 5: 312-317
• 26 Aggarwal D, Pal D, Mitra AK et al. Study of the extent of ocular absorption of acetazolamide from a developed niosomal formulation, by microdialysis sampling of aqueous humor. Int J Pharm 2007; 338: 21-26
• 27 Oswald T, Riley DA. Peripheral nerve carbonic anhydrase activity and chronic acetazolamide treatment of rats. Brain Res 1987; 406: 379-384
• 28 Teppema LJ, Dahan A. Low-dose acetazolamide reduces the hypoxic ventilatory response in the anesthetized cat. Respiratory Physiology & Neurobiology 2004; 140: 43-51
• 29 Douglas Ried L, Carter KA, Ellsworth A. Acetazolamide or dexamethasone for prevention of acute mountain sickness: a meta-analysis. Journal of Wilderness Medicine 1994; 5: 34-48
• 30 Lockwood AH, LaManna JC, Snyder S et al. Effects of acetazolamide and electrical stimulation on cerebral oxidative metabolism as indicated by the cytochrome oxidase redox state. Brain Res 1984; 308: 9-14
• 31 Teppema LJ, Rochette F, Demedts M. Ventilatory response to carbonic anhydrase inhibition in cats: effects of acetazolamide in intact vs peripherally chemodenervated animals. Respir Physiol 1988; 74: 373-382
• 32 Barzegar-Jalali M, Alaei-Beirami M, Javadzadeh Y et al. Comparison of physicochemical characteristics and drug release of diclofenac sodium/eudragit RS100 nanoparticles and solid dispersions. Powder Technol 2012; 219: 211-216
• 33 Barzegar-Jalali M, Valizadeh H, Siahi Shadbad MR et al. Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide). Powder Technol 2010; 197: 150-158
• 34 The United States Pharmacopeia 34:The National Formulary 29, The United States Pharmacopeial Convention, Inc, Rockville 2011
• 35 Maggio RM, Castellano PM, Kaufman TS. A new principal component analysis-based approach for testing “similarity” of drug dissolution profiles. Eur J Pharm Sci 2008; 34: 66-77
• 36 Pillay V, Fassihi R. Evaluation and comparison of dissolution data derived from different modified release dosage forms: an alternative method. J Control Release 1998; 55: 45-55
• 37 Badwan AA, Abumalooh A, Sallam E et al. A sustained release drug delivery system, journal of drug development and industrial pharmacy 1985; 11: 239-256
• 38 Chowdhary KPR. Ramesh KVRNS, studies on microencapsulation of Diltiazem. Indian journal of pharmaceutical sciences 1993; 55: 52-54
• 39 Hwang S-J, Rhee GJ, Lee KM et al. Release characteristics of ibuprofen from excipient-loaded alginate gel beads. Int J Pharm 1995; 116: 125-128
• 40 Ostberg T, Graffner C. Calcium alginate matrices for oral multiple unites administration: III influence of calcium concentration, amount of drug added and alginate characteristics on drug release. Int J Pharm 1994; 111: 271-282
• 41 Javadzadeh Y, Ahadi F, Davaran S et al. Preparation and physicochemical characterization of naproxen/PLGA nanoparticles. Colloids Surf B Biointerfaces 2010; 81: 498-502
• 42 Mohammadi G, Nokhodchi A, Barzegar-Jalali M et al. Physicochemical and anti-bacterial performance characterization of clarithromycin nanoparticles as colloidal drug delivery system. Colloids Surf B Biointerfaces 2011; 88: 39-44
• 43 Adibkia K, Siahi Shadbad MR, Nokhodchi A et al. Piroxicam nanoparticles for ocular delivery: physicochemical characterization and implementation in endotoxin-induced uveitis. J Drug Targeting 2007; 15: 407-416