10. LITERATURE REVIEW OF RESEARCH AND DEVELOPMENT OF PROBIOTIC TABLETS
Main Article Content
Abstract
Probiotics are gaining increasing attention due to their significant benefits to the host. Despite their potential advantages, probiotic dosage forms have not been extensively studied, primarily because of their poor survival through the gastrointestinal tract. Probiotic tablets emerge as a promising delivery system utilized in nutritional products to supplement the natural intestinal flora. These tablets possess the capability to deliver live, functional bacteria in sufficiently large quantities, ensuring effectiveness, and providing protection against the harsh conditions of the gastrointestinal and biliary tract environment, thereby ensuring in vivo protection and maintaining viability during preparation. Various adverse effects that impact the effectiveness of probiotics are associated with preparation methods and user factors. This review primarily focuses on probiotic tablets, delving into factors influencing the existence of microorganisms and the development of formulations for probiotic tablets.
Article Details
Keywords
Probiotic tablet; viability; factor; formulation.
References
[1] E Silva JPS, Sousa SC, Costa P et al., Development
of Probiotic Tablets Using Microparticles:
Viability Studies and Stability Studies. AAPS
PharmSciTech, 14(1), 121–127., 2012.
[2] Govender M, Choonara YE, Kumar P et al., A
review of the advancements in probiotic delivery:
Conventional vs. non-conventional formulations
for intestinal flora supplementation; AAPS
PharmSciTech, 2014, 15, 29–43.
[3] FAO/WHO, Guidelines for the evaluation of
probiotic in food, Joint FAO/WHO working
group report on drafting guidelines for the
evaluation of probiotic in food, 2002.
[4] Kim W-S, Cho C-S, Hong L et al., Oral delivery
of probiotics using pH-sensitive phthalyl
inulin tablets; J Microbiol Biotechnol; 2019;
29(2):200–208.
[5] Gurram S, Jha DK, Shah DS et al., Insights
on the Critical Parameters Affecting the
Probiotic Viability During Stabilization
Process and Formulation Development; AAPS
PharmSciTech. 2021 May 18;22(5):156.
doi: 10.1208/s12249-021-02024-8. PMID:
34008083.
[6] Shu G, Tian M, Chen L et al., Probiotic goat milk
tablets: Formulation optimization and stability
evaluation. LWT, 2019, 108862. doi:10.1016/j.
lwt.2019.108862
[7] Huq T, Vu KD, Riedl B et al., Development
of probiotic tablet using alginate, pectin, and
cellulose nanocrystals as excipients. Cellulose,
23(3), 2016, 1967–1978. doi:10.1007/s10570-
016-0905-2
[8] Vorländer K, Bahlmann L, Kwade A et al.,
Tableting of fluidized bed granules containing
living microorganisms, European Journal of
Pharmaceutics and Biopharmaceutics, 2023.
[9] Sierra-Vega NO, Romañach RJ, Méndez R,
Feed Frame: The Last Processing Step before
the Tablet Compaction in Pharmaceu-tical
Manufacturing. Int. J. Pharm, 2019, 572, 118728.
[10] Vorländer K, Kampen I, Finke JH et al., Along the
Process Chain to Probiotic Tablets: Evaluation
of Mechanical Impacts on Microbial Viability;
Pharmaceutics 2020,12, 66.
[11] Byl E, Bladt P, Lebeer S et al., Importance of
Pressure Plasticity during Compression of
Probiotic Tablet Formulations. Eur. J. Pharm.
Biopharm, 2019,145, 7–11.
[12] Vorländer K, Bahlmann L, Kwade A et al.,
Effect of Process Parameters, Protectants and
Carrier Materials on the Survival of Yeast Cells
during Fluidized Bed Granulation for Tableting,
Pharmaceutics, 2023.
[13] Breitenbach J, Beermann C, Esper GJ,
Comparison of different methods for
microencapsulation of probiotics. Prog. Agric.
Eng. Sci. 2016,12, 63–80.
[14] Yan J, Wu M, Zhao W et al., Effects of probiotics
and its fermented milk on constipation: a
systematic review, Food Science and Human
Wellness, 2023.
[15] Broeckx G, Vandenheuvel D, Claes IJJ et al.,
Drying techniques of probiotic bacteria as an
important step towards the development of novel
pharmabiotics. Int. J. Pharm. 2016,505, 303–318.
[16] El Mafadi S, Picot A, Poncelet D, Modification/
improvement of the Wurster process for drying
or coating sensitive bioactive materials. Minerva
Biotecnol, 2005,17, 231–235.
[17] Zaghari L, Basiri A, Rahimi S, Preparation and
characterization of double-coated probiotic
bacteria via a fluid-bed process: A case study on
Lactobacillus reuteri. Int. J. Food Eng. 2020,16,
108349.
[18] Stummer S, Toegel S, Rabenreither MC et al.,
Fluidized-bed drying as a feasible method for
dehydration of Enterococcus faecium M74. J.
Food Eng; 2012,111, 156–165.
[19] Sun CC, Decoding Powder Tabletability: Roles
of Particle Adhesion and Plasticity. J. Adhes.
Sci. Technol; 2011, 25, 483–499.
[20] Thoorens G, Krier F, Leclercq B et al.,
Microcrystalline Cellulose, a Direct Compression
Binder in a Quality by Design Environment—A
Review. Int. J. Pharm. 2014,473, 64–72.
[21] Klayraung S, Viernstein H, Okonogi S,
Development of Tablets Containing Probiotics:
Effects of Formulation and Processing
Parameters on Bacterial Viability. Int. J. Pharm.
2009,370, 54–60.
[22] Allouche R, Dupont S, Charriau A et al.,
Optimized Tableting for Extremely Oxygen
Sensitive Probiotics Using Direct Compression.
Int. J. Pharm, 2018, 538, 14–20.
[23] Byl E, Jokicevic K, Kiekens S et al., Strain
Specific Differences in Behaviour among
Lacticaseibacillus Rhamnosus Cell Wall Mutants
during Direct Compression. Int. J. Pharm.
2020,588, 119755.
[24] Iswandana R, Putri KSS, Anisa HN et al.,
Formulation of various polysaccharides-based
multicoated tablets containing dexamethasone
and probiotics for inflammatory bowel disease,
Journal of Applied Pharmaceutical Science, 2023.
[25] Blair TC, Buckton G, Bloomfield SF, On the
mechanism of kill of microbial contaminants
during tablet compression. Int. J. Pharm; 1991,
72, 111–115.
[26] Plumpton EJ, Gilbert P, Fell JT, The survival of
microorganisms during tabletting. Int. J. Pharm;
1986, 30, 241–246.
[27] Fassihi AR, Parker MS, Inimical Effects of
Compaction Speed on Microorganisms in
Powder Systems with Dissimilar Compaction
Mechanisms. J. Pharm. Sci. 1987, 76, 466–470.
[28] Vorländer K, Bahlmann L, Kwade A et al.,
Influence of compression kinetics during tableting
of fluidized bed-granulated microorganisms on
microbiological and physical-mechanical tablet
properties, European Journal of Pharmaceutics
and Biopharmaceutics, 2023.
[29] Gurram S, Jha DK, Shah DS et al., Insights
on the Critical Parameters Affecting the
Probiotic Viability During Stabilization
Process and Formulation Development, AAPS
PharmSciTech, 2021.
[30] Yao M, Xie J, Du H et al., Progress in
microencapsulation of probiotics: a review.
Compre Rev Food Sci. 2020;19(2):857–874.
doi: 10.1111/1541-4337.12532
[31] Baral, Kshitis & Bajracharya, Rajiv & Lee
et al., Advancements in the Pharmaceutical
Applications of Probiotics: Dosage Forms and
Formulation Technology. International Journal
of Nanomedicine, 2021, Volume 16. 7535-7556.
10.2147/IJN.S337427.
[32] Urdaneta V, Casadesús J, Interactions between
bacteria and bile salts in the gastrointestinal and
hepatobiliary tracts. Front Med. 2017;4:163. doi:
10.3389/fmed.2017.00163.
[33] Grenier D, Effect of proteolytic enzymes on
the lysis and growth of oral bacteria. Oral
Microbiol Immunol. 1994;9(4):224–228. doi:76
10.1111/j.1399-302X.1994.tb00062.x.
[34] Pliszczak D, Bourgeois S, Bordes C et al.,
Improvement of an encapsulation process for
the preparation of pro- and prebiotics-loaded
bioadhesive microparticles by using experimental
design. Eur J Pharm Sci. 2011;44(1):83–92. doi:
10.1016/j.ejps.2011.06.011.
[35] Merkus FW, Verhoef JC, Schipper NG et
al., Nasal mucociliary clearance as a factor
in nasal drug delivery. Adv Drug Deliv Rev.
1998;29(1–2):13–38. doi: 10.1016/S0169-
409X(97)00059-8.
[36] Serralheiro A, Alves G, Sousa J et al., Nose as
a route for drug delivery. In: Önerci TM, editor.
Nasal Physiology and Pathophysiology of Nasal
Disorders. 1st ed. Berlin: Springer; 2013:191–215.
[37] De Rudder C, Garcia-Tímermans C, De Boeck
I et al., Lacticaseibacillus casei AMBR2
modulates the epithelial barrier function and
immune response in a donor-derived nasal
microbiota manner. Sci Rep. 2020;10(1):16939.
doi: 10.1038/s41598-020-73857-9.
[38] Terpou A, Papadaki A, Lappa IK et al., Probiotics
in food systems: significance and emerging
strategies towards improved viability and
delivery of enhanced beneficial value. Nutrients;
2019;11(7):1591. doi: 10.3390/nu11071591.
[39] Stanbury PF, Whitaker A, Hall SJ, The recovery
and purification of fermentation products. In:
Stanbury PF, Whitaker A, Hall SJ, editors.
Principles of Fermentation Technology. 3rd ed.
Oxford: Butterworth-Heinemann; 2017:619–686.
[40] Blair TC, Buckton G, Bloomfield SF, On the
mechanism of kill of microbial contaminants
during tablet compression. Int J Pharm.
1991;72(2):111–115. doi: 10.1016/0378-
5173(91)90048-S.
[41] Plumpton EJ, Gilbert P, Fell JT, The survival of
microorganisms during tabletting. Int J Pharm.
1986;30(2–3):241–246. doi: 10.1016/0378-
5173(86)90086-4.
[42] Mills S, Stanton C, Fitzgerald GF et al.,
Enhancing the stress responses of probiotics for
a lifestyle from gut to product and back again.
Microb Cell Fact. 2011;10(Suppl 1):S19–S19.
doi: 10.1186/1475-2859-10-S1-S19.
[43] Ketaubon P, Prapagdee B, Enhancing cadmium
phytoremediation of Chlorophytum comosum
(Thunb.) Jacques by applying cadmium-resistant
bacterial tablet, Environmental Science and
Pollution Research, Article in Press 2023
[44] Kaur R, Simnani FZ, Singh S, Enhancement of
Probiotics for Functional Food ( Book Chapter),
Recent Advances in Food Biotechnology, 2022.
[45] Das NC, Patra R, Dey A et al., Probiotics as
Efficacious Therapeutic Option for Treating
Gut-Related Diseases: Molecular and
Immunobiological Perspectives (Book Chapter),
Prebiotics, Probiotics and Nutraceuticals, 2022
[46] Sreeja V, Prajapati JB, Probiotic Formulations:
Application and Status as Pharmaceuticals—A
Review. Probiotics and Antimicrobial Proteins,
5(2), 2013, 81–91. doi:10.1007/s12602-013-9126-2
[47] Plumpton EJ, Gilbert P, Fell JT, Effect of spatial
distribution of contaminant microorganisms
within tablet formulations on subsequent
inactivation through compaction. Int. J. Pharm,
1986, 30, 237–240.
[48] Chan ES, Zhang Z, Encapsulation of probiotic
bacteria Lactobacillus acidophilus by direct
compression. Trans IChemE 80 (part C), 2002,
pp 78–82
[49] Maggi L, Mastromarino P, Macchia S et al.,
Technological and biological evaluation of
tablets containing different strains of lactobacilli
for vaginal administration. Eur J Pharm Biopharm
50:389–395, 2000.
[50] Mohd AA, Mimi SAM, Design and optimization
of a probiotic tablet for gastrointestinal
tolerance by a simplex-centroid mixture, Drug
Development and Industrial Pharmacy, 2020.77
[51] Sierra-Vega NO, Romañach RJ, Méndez R,
Feed Frame: The Last Processing Step before
the Tablet Compaction in Pharmaceu-tical
Manufacturing. Int. J. Pharm, 2019,572, 118728.
[52] Vorländer K, Kampen I, Finke JH et al., Along the
Process Chain to Probiotic Tablets: Evaluation
of Mechanical Impacts on Microbial Viability;
Pharmaceutics 2020,12, 66.
[53] Byl E, Bladt P, Lebeer S et al., Importance of
Pressure Plasticity during Compression of
Probiotic Tablet Formulations. Eur. J. Pharm.
Biopharm. 2019,145, 7–11.
[54] Maggi L, Mastromarino P, Macchia S et al.,
Technological and biological evaluation of
tablets containing different strains of lactobacilli
for vaginal administration. Eur J Pharm
Biopharm; 2000;50(3):389–395
[55] Azhar MA, Munaim MSA, Design and
optimization of a probiotic tablet for
gastrointestinal tolerance by a simplex-centroid
mixture. Drug Development and Industrial
Pharmacy, 47(2), 2020, 189–196.
of Probiotic Tablets Using Microparticles:
Viability Studies and Stability Studies. AAPS
PharmSciTech, 14(1), 121–127., 2012.
[2] Govender M, Choonara YE, Kumar P et al., A
review of the advancements in probiotic delivery:
Conventional vs. non-conventional formulations
for intestinal flora supplementation; AAPS
PharmSciTech, 2014, 15, 29–43.
[3] FAO/WHO, Guidelines for the evaluation of
probiotic in food, Joint FAO/WHO working
group report on drafting guidelines for the
evaluation of probiotic in food, 2002.
[4] Kim W-S, Cho C-S, Hong L et al., Oral delivery
of probiotics using pH-sensitive phthalyl
inulin tablets; J Microbiol Biotechnol; 2019;
29(2):200–208.
[5] Gurram S, Jha DK, Shah DS et al., Insights
on the Critical Parameters Affecting the
Probiotic Viability During Stabilization
Process and Formulation Development; AAPS
PharmSciTech. 2021 May 18;22(5):156.
doi: 10.1208/s12249-021-02024-8. PMID:
34008083.
[6] Shu G, Tian M, Chen L et al., Probiotic goat milk
tablets: Formulation optimization and stability
evaluation. LWT, 2019, 108862. doi:10.1016/j.
lwt.2019.108862
[7] Huq T, Vu KD, Riedl B et al., Development
of probiotic tablet using alginate, pectin, and
cellulose nanocrystals as excipients. Cellulose,
23(3), 2016, 1967–1978. doi:10.1007/s10570-
016-0905-2
[8] Vorländer K, Bahlmann L, Kwade A et al.,
Tableting of fluidized bed granules containing
living microorganisms, European Journal of
Pharmaceutics and Biopharmaceutics, 2023.
[9] Sierra-Vega NO, Romañach RJ, Méndez R,
Feed Frame: The Last Processing Step before
the Tablet Compaction in Pharmaceu-tical
Manufacturing. Int. J. Pharm, 2019, 572, 118728.
[10] Vorländer K, Kampen I, Finke JH et al., Along the
Process Chain to Probiotic Tablets: Evaluation
of Mechanical Impacts on Microbial Viability;
Pharmaceutics 2020,12, 66.
[11] Byl E, Bladt P, Lebeer S et al., Importance of
Pressure Plasticity during Compression of
Probiotic Tablet Formulations. Eur. J. Pharm.
Biopharm, 2019,145, 7–11.
[12] Vorländer K, Bahlmann L, Kwade A et al.,
Effect of Process Parameters, Protectants and
Carrier Materials on the Survival of Yeast Cells
during Fluidized Bed Granulation for Tableting,
Pharmaceutics, 2023.
[13] Breitenbach J, Beermann C, Esper GJ,
Comparison of different methods for
microencapsulation of probiotics. Prog. Agric.
Eng. Sci. 2016,12, 63–80.
[14] Yan J, Wu M, Zhao W et al., Effects of probiotics
and its fermented milk on constipation: a
systematic review, Food Science and Human
Wellness, 2023.
[15] Broeckx G, Vandenheuvel D, Claes IJJ et al.,
Drying techniques of probiotic bacteria as an
important step towards the development of novel
pharmabiotics. Int. J. Pharm. 2016,505, 303–318.
[16] El Mafadi S, Picot A, Poncelet D, Modification/
improvement of the Wurster process for drying
or coating sensitive bioactive materials. Minerva
Biotecnol, 2005,17, 231–235.
[17] Zaghari L, Basiri A, Rahimi S, Preparation and
characterization of double-coated probiotic
bacteria via a fluid-bed process: A case study on
Lactobacillus reuteri. Int. J. Food Eng. 2020,16,
108349.
[18] Stummer S, Toegel S, Rabenreither MC et al.,
Fluidized-bed drying as a feasible method for
dehydration of Enterococcus faecium M74. J.
Food Eng; 2012,111, 156–165.
[19] Sun CC, Decoding Powder Tabletability: Roles
of Particle Adhesion and Plasticity. J. Adhes.
Sci. Technol; 2011, 25, 483–499.
[20] Thoorens G, Krier F, Leclercq B et al.,
Microcrystalline Cellulose, a Direct Compression
Binder in a Quality by Design Environment—A
Review. Int. J. Pharm. 2014,473, 64–72.
[21] Klayraung S, Viernstein H, Okonogi S,
Development of Tablets Containing Probiotics:
Effects of Formulation and Processing
Parameters on Bacterial Viability. Int. J. Pharm.
2009,370, 54–60.
[22] Allouche R, Dupont S, Charriau A et al.,
Optimized Tableting for Extremely Oxygen
Sensitive Probiotics Using Direct Compression.
Int. J. Pharm, 2018, 538, 14–20.
[23] Byl E, Jokicevic K, Kiekens S et al., Strain
Specific Differences in Behaviour among
Lacticaseibacillus Rhamnosus Cell Wall Mutants
during Direct Compression. Int. J. Pharm.
2020,588, 119755.
[24] Iswandana R, Putri KSS, Anisa HN et al.,
Formulation of various polysaccharides-based
multicoated tablets containing dexamethasone
and probiotics for inflammatory bowel disease,
Journal of Applied Pharmaceutical Science, 2023.
[25] Blair TC, Buckton G, Bloomfield SF, On the
mechanism of kill of microbial contaminants
during tablet compression. Int. J. Pharm; 1991,
72, 111–115.
[26] Plumpton EJ, Gilbert P, Fell JT, The survival of
microorganisms during tabletting. Int. J. Pharm;
1986, 30, 241–246.
[27] Fassihi AR, Parker MS, Inimical Effects of
Compaction Speed on Microorganisms in
Powder Systems with Dissimilar Compaction
Mechanisms. J. Pharm. Sci. 1987, 76, 466–470.
[28] Vorländer K, Bahlmann L, Kwade A et al.,
Influence of compression kinetics during tableting
of fluidized bed-granulated microorganisms on
microbiological and physical-mechanical tablet
properties, European Journal of Pharmaceutics
and Biopharmaceutics, 2023.
[29] Gurram S, Jha DK, Shah DS et al., Insights
on the Critical Parameters Affecting the
Probiotic Viability During Stabilization
Process and Formulation Development, AAPS
PharmSciTech, 2021.
[30] Yao M, Xie J, Du H et al., Progress in
microencapsulation of probiotics: a review.
Compre Rev Food Sci. 2020;19(2):857–874.
doi: 10.1111/1541-4337.12532
[31] Baral, Kshitis & Bajracharya, Rajiv & Lee
et al., Advancements in the Pharmaceutical
Applications of Probiotics: Dosage Forms and
Formulation Technology. International Journal
of Nanomedicine, 2021, Volume 16. 7535-7556.
10.2147/IJN.S337427.
[32] Urdaneta V, Casadesús J, Interactions between
bacteria and bile salts in the gastrointestinal and
hepatobiliary tracts. Front Med. 2017;4:163. doi:
10.3389/fmed.2017.00163.
[33] Grenier D, Effect of proteolytic enzymes on
the lysis and growth of oral bacteria. Oral
Microbiol Immunol. 1994;9(4):224–228. doi:76
10.1111/j.1399-302X.1994.tb00062.x.
[34] Pliszczak D, Bourgeois S, Bordes C et al.,
Improvement of an encapsulation process for
the preparation of pro- and prebiotics-loaded
bioadhesive microparticles by using experimental
design. Eur J Pharm Sci. 2011;44(1):83–92. doi:
10.1016/j.ejps.2011.06.011.
[35] Merkus FW, Verhoef JC, Schipper NG et
al., Nasal mucociliary clearance as a factor
in nasal drug delivery. Adv Drug Deliv Rev.
1998;29(1–2):13–38. doi: 10.1016/S0169-
409X(97)00059-8.
[36] Serralheiro A, Alves G, Sousa J et al., Nose as
a route for drug delivery. In: Önerci TM, editor.
Nasal Physiology and Pathophysiology of Nasal
Disorders. 1st ed. Berlin: Springer; 2013:191–215.
[37] De Rudder C, Garcia-Tímermans C, De Boeck
I et al., Lacticaseibacillus casei AMBR2
modulates the epithelial barrier function and
immune response in a donor-derived nasal
microbiota manner. Sci Rep. 2020;10(1):16939.
doi: 10.1038/s41598-020-73857-9.
[38] Terpou A, Papadaki A, Lappa IK et al., Probiotics
in food systems: significance and emerging
strategies towards improved viability and
delivery of enhanced beneficial value. Nutrients;
2019;11(7):1591. doi: 10.3390/nu11071591.
[39] Stanbury PF, Whitaker A, Hall SJ, The recovery
and purification of fermentation products. In:
Stanbury PF, Whitaker A, Hall SJ, editors.
Principles of Fermentation Technology. 3rd ed.
Oxford: Butterworth-Heinemann; 2017:619–686.
[40] Blair TC, Buckton G, Bloomfield SF, On the
mechanism of kill of microbial contaminants
during tablet compression. Int J Pharm.
1991;72(2):111–115. doi: 10.1016/0378-
5173(91)90048-S.
[41] Plumpton EJ, Gilbert P, Fell JT, The survival of
microorganisms during tabletting. Int J Pharm.
1986;30(2–3):241–246. doi: 10.1016/0378-
5173(86)90086-4.
[42] Mills S, Stanton C, Fitzgerald GF et al.,
Enhancing the stress responses of probiotics for
a lifestyle from gut to product and back again.
Microb Cell Fact. 2011;10(Suppl 1):S19–S19.
doi: 10.1186/1475-2859-10-S1-S19.
[43] Ketaubon P, Prapagdee B, Enhancing cadmium
phytoremediation of Chlorophytum comosum
(Thunb.) Jacques by applying cadmium-resistant
bacterial tablet, Environmental Science and
Pollution Research, Article in Press 2023
[44] Kaur R, Simnani FZ, Singh S, Enhancement of
Probiotics for Functional Food ( Book Chapter),
Recent Advances in Food Biotechnology, 2022.
[45] Das NC, Patra R, Dey A et al., Probiotics as
Efficacious Therapeutic Option for Treating
Gut-Related Diseases: Molecular and
Immunobiological Perspectives (Book Chapter),
Prebiotics, Probiotics and Nutraceuticals, 2022
[46] Sreeja V, Prajapati JB, Probiotic Formulations:
Application and Status as Pharmaceuticals—A
Review. Probiotics and Antimicrobial Proteins,
5(2), 2013, 81–91. doi:10.1007/s12602-013-9126-2
[47] Plumpton EJ, Gilbert P, Fell JT, Effect of spatial
distribution of contaminant microorganisms
within tablet formulations on subsequent
inactivation through compaction. Int. J. Pharm,
1986, 30, 237–240.
[48] Chan ES, Zhang Z, Encapsulation of probiotic
bacteria Lactobacillus acidophilus by direct
compression. Trans IChemE 80 (part C), 2002,
pp 78–82
[49] Maggi L, Mastromarino P, Macchia S et al.,
Technological and biological evaluation of
tablets containing different strains of lactobacilli
for vaginal administration. Eur J Pharm Biopharm
50:389–395, 2000.
[50] Mohd AA, Mimi SAM, Design and optimization
of a probiotic tablet for gastrointestinal
tolerance by a simplex-centroid mixture, Drug
Development and Industrial Pharmacy, 2020.77
[51] Sierra-Vega NO, Romañach RJ, Méndez R,
Feed Frame: The Last Processing Step before
the Tablet Compaction in Pharmaceu-tical
Manufacturing. Int. J. Pharm, 2019,572, 118728.
[52] Vorländer K, Kampen I, Finke JH et al., Along the
Process Chain to Probiotic Tablets: Evaluation
of Mechanical Impacts on Microbial Viability;
Pharmaceutics 2020,12, 66.
[53] Byl E, Bladt P, Lebeer S et al., Importance of
Pressure Plasticity during Compression of
Probiotic Tablet Formulations. Eur. J. Pharm.
Biopharm. 2019,145, 7–11.
[54] Maggi L, Mastromarino P, Macchia S et al.,
Technological and biological evaluation of
tablets containing different strains of lactobacilli
for vaginal administration. Eur J Pharm
Biopharm; 2000;50(3):389–395
[55] Azhar MA, Munaim MSA, Design and
optimization of a probiotic tablet for
gastrointestinal tolerance by a simplex-centroid
mixture. Drug Development and Industrial
Pharmacy, 47(2), 2020, 189–196.