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Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD

Yıl 2023, Cilt: 27 Sayı: 5, 2067 - 2078, 28.06.2025

Rajani Thoutreddy Koteswara Rao Gsn Narender Malothu Chakravarthi Guntupalli Pavani Sriram Rajasekhar Reddy Alavala

Öz

Cubosomes, which are modified cubic phase systems, are looking very promising as a method of delivering both hydrophilic and lipophilic drugs. Transdermal delivery of cubosomes is currently gaining more importance over conventional topical delivery of drugs. The proposed study aimed to produce Lidocaine hydrochloride loaded cubosomes. This study was designed to prepare various formulations of Lidocaine nano cubsomal dispersions at different concentrations of lipid and stabilizer using optimization technique. For the purpose of prolonging the duration of the local anaesthetic action, Lidocaine-loaded cubosomes were developed by bottom up method utilizing Glyceryl mono oleate and Poloxamer 407 in various ratios using the "Quality by Design" approach, 32 factorial design employing statistical software. Within the confidence intervals, the 32 statistical design was effective at forecasting the optimized formulation's composition. Surface morphology, particle size, drug content, poly dispersibility index, zeta potential, entrapment efficiency, and in vitro drug release studies were conducted on the prepared formulations. Several mathematical models were used to conduct and assess an in vitro drug release investigation. The maximal entrapment efficiency for the LH8 formulation, which was validated to have optimum cubosomes dispersion, was reported to be 78 % with vesicle size as 150 nm, Zeta potential 21.5 mV and Poly Dispersibility Index as 0.08 along with an in vitro drug release 80.03 % by the end of 24 hours. A stable dispersion with appreciable results of evaluation parameters of cubosomal dispersion was conferred with formulation LH8. Hence from amongst the nine formulations developed, it is concluded that LH8 is selected as the optimized dispersion to be incorporated into a gel formulation.

Anahtar Kelimeler

Lidocaine Hydrochloride Cubosomes Design of Experiment Quality by Design Glyceryl mono oleate Poloxamer

Kaynakça

  • [1] Tekade AR, Avhad GD. A review on cubosome: a novel approach for drug delivery. Int. J. Pharm. Sci. Res. 2022; 13 (2): 579-588. https://doi.org/10.13040/IJPSR.0975-8232.13(2).579-588.
  • [2] Sherif AG, Omar HG, Hamdy A. Cubosomes: composition, preparation and drug delivery applications. J. Adv. Biomed. Pharm. Appl. 2020; 3:1-9. https://dx.doi.org/10.21608/jabps.2019.16887.1057.
  • [3] Nilesh RR, Pramod BK. Cubosomes: a vehicle for delivery of various therapeutic agents. MOJ Toxicol. 2018; 4(1): 19-21. https://doi.org/10.15406/mojt.2018.04.00083.
  • [4] Kaur SD, Singh G, Singh G, Singhal K, Kant S, Bedi N. Cubosomes as Potential Nanocarrier for Drug Delivery: A Comprehensive Review. J. Pharm. Res. Int. 2021; 33(31B): 118-135. https://doi.org/10.9734/jpri/2021/v33i31B31698.
  • [5] Rajani T, Umasankar K, Rao GSNK, Rajasekhar A, Chakravarthy G, Alekhya M. Fabrication and evaluation of Lidocaine Hydrochloride cubosomes. Res. J. Pharm. Technol. 2021;14(10): 5288-5302. https://doi.org/10.52711/0974-360X.2021.00922.
  • [6] Zhao X, Sun Y, Li Z. Topical anesthesia therapy using lidocaine-loaded nanostructured lipid carriers: tocopheryl polyethylene glycol 1000 succinate-modified transdermal delivery system. Drug Des, Devel. Ther. 2018; 12: 4231–4240. https://doi.org/10.2147%2FDDDT.S187177.
  • [7] Soraya B, Saeed G, Soodabeh D, Maryam K, Hamed H. Nanoethosomes for Dermal Delivery of Lidocaine. Adv. Pharm. Bull. 2015; 5(4): 549-556. https://doi.org/10.15171%2Fapb.2015.074.
  • [8] Dhadwal A, Sharma DR, Pandit V, Ashawat MS, Kumar P. Cubosomes: A Novel Carrier for Transdermal Drug Delivery. J. Drug. Deliv. Ther. 2020; 10(1):123-130. https://doi.org/10.22270/jddt.v10i1.3814.
  • [9] Lakshmi PY, Pavan KJ, Mohan VM, Anand A. Cubosomes: A novel drug delivery system. Int. J. Res. Ayurveda Pharm. 2020; 11 (5): 198-204. https://doi.org/10.7897/2277-4343.1105169.
  • [10] Anan Y, Huiling M. Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles. Acta Pharm. Sin. B. 2021; 11(4): 871–885. https://doi.org/10.1016/j.apsb.2021.02.013.
  • [11] Tejashree W, Dabholkar N, Gorantla S, Rapalli VK, Singhvi G. Quality by design in the formulation and optimization of liquid crystalline nanoparticles (LCNPs): A risk based industrial approach. Biomed. Pharmacother. 2021; 141: 1-15. https://doi.org/10.1016/j.biopha.2021.111940.
  • [12] Fahima H, Mohamed N, Mohamed Y. Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers. J. Adv. Res. 2018; 2(2): 95-103. https://dx.doi.org/10.21608/aprh.2018.5828.
  • [13] Marzuka K, Mohammed HD. Development of inhalable cubosome nanoparticles of Nystatin for effective management of Invasive Pulmonary Aspergillosis. Istanbul J. Pharm. 50 (3): 224-237. https://doi.org/10.26650/IstanbulJPharm.2020.0006.
  • [14] Yong T, Jian L, Jin Z, Na Z, Hong Z, Lili L, Lingvi S. Folic acid tragetted etoposide cubosomes for Theranostic application of cancer cell imaging and therapy. Med. Sci. Monit. 2017; 23: 2426–2435. https://doi.org/10.12659/msm.904683.
  • [15] Thoutreddy R, Gullapudi M, Bonepally R. Fabrication and evaluation of Dexamethasone loaded cubosomes. Res. J. Pharm. Technol. 2020; 13(2): 709-714. https://doi.org/10.5958/0974-360X.2020.00135.3.
  • [16] Ananda K. CH, Madhubabu A, Padmanabha RA, Vasudha B, Vinod KY. Design, Formulation, In-Vitro and Ex-Vivo Evaluation of Atazanavir Loaded Cubosomal Gel. Biointerface Res. Appl. Chem. 2021; 11(4): 12037-12054. https://doi.org/10.33263/BRIAC114.1203712054.
  • [17] Sriram P, Yamsani MR, Yamsani SK. Use of Box-Behnken Experimental design for Optimization of process variables in Iontophoretic delivery of Repaglinide. J. Young Pharm. 2016; 8(4): 35-355. https://doi.org/10.5530/jyp.2016.4.10.
  • [18] Hadel AE, Areej HA. Nanostructured liquid crystalline formulation as a remarkable new drug delivery system of anti-epileptic drugs for treating children patients. Saudi Pharm. J. 2018; 26(6): 790-800. https://doi.org/10.1016/j.jsps.2018.04.004.
  • [19] Rapalli VK, Banerjee S, Khan S, Jha PN, Gupta G, Dua K, Hasnain MS, Nayak AK, Dubey SK, Singhvi G. QbD-driven formulation development and evaluation of topical hydrogel containing ketoconazole loaded cubosomes. Mater Sci Eng C Mater Biological Appl. 2021; 119: 111548. https://doi.org/10.1016/j.msec.2020.111548.
  • [20] Saffron JB, Elly KB, Karren JE. Bottom up cubosome synthesis without organic solvents. J. Colloid Interf. Sci. 2021; 601: 98-105. https://doi.org/10.1016/j.jcis.2021.05.072.
  • [21] Hassaan U, Habibah AW, Amirah MG, Hafsa T, Waqas A. Cubosomes: Design, Development and Tumour Targeted Drug Delivery Applications. Polym. J. 2022; 14(15): 1-18. https://doi.org/10.3390/polym14153118.
  • [22] Vaishali T, Vaishali K, Lalji B, Mukesh G, Tejal G, Nirav P. Development and characterization of novel hydrogel containing anti-microbial drug for treatment of burns. Int. J. Pharm. Res. 2016; 6(3): 158-163. https://doi.org/10.4103/2230-973x.187343.
  • [23] Pavani S, Mounika K, Naresh K. Formulation and evaluation of Acyclovir Microspheres. Iraqi. J. Pharm. Sci. 2018; 27(1): 1-7. https://doi.org/10.31351/vol27iss1pp1-7
  • [24] Bhaskar K, Sunil J, Satveer J. Formulation and evaluation of Resveratrol loaded cubosomal nanoformulation for topical delivery. Curr. Drug Deliv. 2021; 18(5): 607-619. http://doi.org/10.2174/1567201817666200902150646.
  • [25] Omar SM, Ismail A, Hassanin KD, Dawoud SH. Formulation and Evaluation of Cubosomes as Skin Retentive System for Topical Delivery of Clotrimazole. J. Adv. Pharm. Res. 2019; 3(2), 68-82. https://doi.org/10.21608/APRH.2019.9839.1079.
  • [26] Peng X, Zhou Y, Han K, Qin L, Dian L, Li G, Pan X, Wu C. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin. Drug Des. Devel. Ther. 2015; 9:4209-4218. https://doi.org/10.2147%2FDDDT.S86370.
  • [27] Sadeq AS, Nidhal KM. Optimization and In Vitro evaluation of the release of class II drug from its nanocubosomal dispersion. Int. J. App. Pharm. 2019; 11(2): 86-90. https://doi.org/10.22159/ijap.2019v11i2.30582.
  • [28] Flak DK, Adamski V, Nowaczyk G, Szutkowski K, Synowitz M, Jurga S, Held-Feindt J. AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy. Int. J. Nanomedicine. 2020; 15: 7415-7431. https://doi.org/10.2147/IJN.S265061.
  • [29] Mohamed N, Mohamed KG, Ahmed A. In Vitro and In Vivo evaluation of cubosomes containing 5-Fluorouracil for liver targeting. Acta Pharm. Sin. B. 2015; 5(1): 79-88. https://doi.org/10.1016%2Fj.apsb.2014.12.001.
  • [30] Hanan ME, Alia B, Nevine SA, Nihal ES. Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine. Chem. Pharm. Bull. 2018; 66(12): 1165-1173. https://doi.org/10.1248/cpb.c18-00615.
  • [31] Alaa EE, Salwa S, Mahmoud G. Formulation and evaluation of cubosomes drug delivery system for treatment of Glaucoma: Ex vivo permeation and in vivo pharmacodynamic study. J. Drug Deliv. Sci. Technol. 2019; 52. http://dx.doi.org/10.1016/j.jddst.2019.04.036.
  • [32] Hoda ET, Islam AK, Heba MS. Novel cubosome based system for ocular delivery of Acetazolamide. Drug Deliv. 2021; 1: 2177-2186. https://doi.org/10.1080%2F10717544.2021.1989090.
  • [33] Muheem A, Shakeel F, Warsi M, Jain G, Ahmad F. A Combinatorial Statistical Design Approach to Optimize the Nanostructured Cubosomal Carrier System for Oral Delivery of Ubidecarenone for Management of Doxorubicin-Induced Cardiotoxicity. J. Pharm. Sci. 2017; 106(10): 1-17. https://doi.org/10.1016/j.xphs.2017.05.026.
  • [34] Hosny KM. Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation. Int. J. Nanomedicine. 2020; 15: 5113-5129. https://doi.org/10.2147/IJN.S261855.
  • [35] Ankit A, Prakash G, Vinay CH. Determination of Mucoadhesive behaviour of Timolol maleate liquid crystalline cubogel by different Techniques. Asian J. Pharm. Res. 2019; 9(1): 7-11. https://doi.org/10.5958/2231-5691.2019.00002.9.

Yıl 2023, Cilt: 27 Sayı: 5, 2067 - 2078, 28.06.2025

Rajani Thoutreddy Koteswara Rao Gsn Narender Malothu Chakravarthi Guntupalli Pavani Sriram Rajasekhar Reddy Alavala

Öz

Kaynakça

  • [1] Tekade AR, Avhad GD. A review on cubosome: a novel approach for drug delivery. Int. J. Pharm. Sci. Res. 2022; 13 (2): 579-588. https://doi.org/10.13040/IJPSR.0975-8232.13(2).579-588.
  • [2] Sherif AG, Omar HG, Hamdy A. Cubosomes: composition, preparation and drug delivery applications. J. Adv. Biomed. Pharm. Appl. 2020; 3:1-9. https://dx.doi.org/10.21608/jabps.2019.16887.1057.
  • [3] Nilesh RR, Pramod BK. Cubosomes: a vehicle for delivery of various therapeutic agents. MOJ Toxicol. 2018; 4(1): 19-21. https://doi.org/10.15406/mojt.2018.04.00083.
  • [4] Kaur SD, Singh G, Singh G, Singhal K, Kant S, Bedi N. Cubosomes as Potential Nanocarrier for Drug Delivery: A Comprehensive Review. J. Pharm. Res. Int. 2021; 33(31B): 118-135. https://doi.org/10.9734/jpri/2021/v33i31B31698.
  • [5] Rajani T, Umasankar K, Rao GSNK, Rajasekhar A, Chakravarthy G, Alekhya M. Fabrication and evaluation of Lidocaine Hydrochloride cubosomes. Res. J. Pharm. Technol. 2021;14(10): 5288-5302. https://doi.org/10.52711/0974-360X.2021.00922.
  • [6] Zhao X, Sun Y, Li Z. Topical anesthesia therapy using lidocaine-loaded nanostructured lipid carriers: tocopheryl polyethylene glycol 1000 succinate-modified transdermal delivery system. Drug Des, Devel. Ther. 2018; 12: 4231–4240. https://doi.org/10.2147%2FDDDT.S187177.
  • [7] Soraya B, Saeed G, Soodabeh D, Maryam K, Hamed H. Nanoethosomes for Dermal Delivery of Lidocaine. Adv. Pharm. Bull. 2015; 5(4): 549-556. https://doi.org/10.15171%2Fapb.2015.074.
  • [8] Dhadwal A, Sharma DR, Pandit V, Ashawat MS, Kumar P. Cubosomes: A Novel Carrier for Transdermal Drug Delivery. J. Drug. Deliv. Ther. 2020; 10(1):123-130. https://doi.org/10.22270/jddt.v10i1.3814.
  • [9] Lakshmi PY, Pavan KJ, Mohan VM, Anand A. Cubosomes: A novel drug delivery system. Int. J. Res. Ayurveda Pharm. 2020; 11 (5): 198-204. https://doi.org/10.7897/2277-4343.1105169.
  • [10] Anan Y, Huiling M. Recent advances in drug delivery applications of cubosomes, hexosomes, and solid lipid nanoparticles. Acta Pharm. Sin. B. 2021; 11(4): 871–885. https://doi.org/10.1016/j.apsb.2021.02.013.
  • [11] Tejashree W, Dabholkar N, Gorantla S, Rapalli VK, Singhvi G. Quality by design in the formulation and optimization of liquid crystalline nanoparticles (LCNPs): A risk based industrial approach. Biomed. Pharmacother. 2021; 141: 1-15. https://doi.org/10.1016/j.biopha.2021.111940.
  • [12] Fahima H, Mohamed N, Mohamed Y. Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers. J. Adv. Res. 2018; 2(2): 95-103. https://dx.doi.org/10.21608/aprh.2018.5828.
  • [13] Marzuka K, Mohammed HD. Development of inhalable cubosome nanoparticles of Nystatin for effective management of Invasive Pulmonary Aspergillosis. Istanbul J. Pharm. 50 (3): 224-237. https://doi.org/10.26650/IstanbulJPharm.2020.0006.
  • [14] Yong T, Jian L, Jin Z, Na Z, Hong Z, Lili L, Lingvi S. Folic acid tragetted etoposide cubosomes for Theranostic application of cancer cell imaging and therapy. Med. Sci. Monit. 2017; 23: 2426–2435. https://doi.org/10.12659/msm.904683.
  • [15] Thoutreddy R, Gullapudi M, Bonepally R. Fabrication and evaluation of Dexamethasone loaded cubosomes. Res. J. Pharm. Technol. 2020; 13(2): 709-714. https://doi.org/10.5958/0974-360X.2020.00135.3.
  • [16] Ananda K. CH, Madhubabu A, Padmanabha RA, Vasudha B, Vinod KY. Design, Formulation, In-Vitro and Ex-Vivo Evaluation of Atazanavir Loaded Cubosomal Gel. Biointerface Res. Appl. Chem. 2021; 11(4): 12037-12054. https://doi.org/10.33263/BRIAC114.1203712054.
  • [17] Sriram P, Yamsani MR, Yamsani SK. Use of Box-Behnken Experimental design for Optimization of process variables in Iontophoretic delivery of Repaglinide. J. Young Pharm. 2016; 8(4): 35-355. https://doi.org/10.5530/jyp.2016.4.10.
  • [18] Hadel AE, Areej HA. Nanostructured liquid crystalline formulation as a remarkable new drug delivery system of anti-epileptic drugs for treating children patients. Saudi Pharm. J. 2018; 26(6): 790-800. https://doi.org/10.1016/j.jsps.2018.04.004.
  • [19] Rapalli VK, Banerjee S, Khan S, Jha PN, Gupta G, Dua K, Hasnain MS, Nayak AK, Dubey SK, Singhvi G. QbD-driven formulation development and evaluation of topical hydrogel containing ketoconazole loaded cubosomes. Mater Sci Eng C Mater Biological Appl. 2021; 119: 111548. https://doi.org/10.1016/j.msec.2020.111548.
  • [20] Saffron JB, Elly KB, Karren JE. Bottom up cubosome synthesis without organic solvents. J. Colloid Interf. Sci. 2021; 601: 98-105. https://doi.org/10.1016/j.jcis.2021.05.072.
  • [21] Hassaan U, Habibah AW, Amirah MG, Hafsa T, Waqas A. Cubosomes: Design, Development and Tumour Targeted Drug Delivery Applications. Polym. J. 2022; 14(15): 1-18. https://doi.org/10.3390/polym14153118.
  • [22] Vaishali T, Vaishali K, Lalji B, Mukesh G, Tejal G, Nirav P. Development and characterization of novel hydrogel containing anti-microbial drug for treatment of burns. Int. J. Pharm. Res. 2016; 6(3): 158-163. https://doi.org/10.4103/2230-973x.187343.
  • [23] Pavani S, Mounika K, Naresh K. Formulation and evaluation of Acyclovir Microspheres. Iraqi. J. Pharm. Sci. 2018; 27(1): 1-7. https://doi.org/10.31351/vol27iss1pp1-7
  • [24] Bhaskar K, Sunil J, Satveer J. Formulation and evaluation of Resveratrol loaded cubosomal nanoformulation for topical delivery. Curr. Drug Deliv. 2021; 18(5): 607-619. http://doi.org/10.2174/1567201817666200902150646.
  • [25] Omar SM, Ismail A, Hassanin KD, Dawoud SH. Formulation and Evaluation of Cubosomes as Skin Retentive System for Topical Delivery of Clotrimazole. J. Adv. Pharm. Res. 2019; 3(2), 68-82. https://doi.org/10.21608/APRH.2019.9839.1079.
  • [26] Peng X, Zhou Y, Han K, Qin L, Dian L, Li G, Pan X, Wu C. Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin. Drug Des. Devel. Ther. 2015; 9:4209-4218. https://doi.org/10.2147%2FDDDT.S86370.
  • [27] Sadeq AS, Nidhal KM. Optimization and In Vitro evaluation of the release of class II drug from its nanocubosomal dispersion. Int. J. App. Pharm. 2019; 11(2): 86-90. https://doi.org/10.22159/ijap.2019v11i2.30582.
  • [28] Flak DK, Adamski V, Nowaczyk G, Szutkowski K, Synowitz M, Jurga S, Held-Feindt J. AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy. Int. J. Nanomedicine. 2020; 15: 7415-7431. https://doi.org/10.2147/IJN.S265061.
  • [29] Mohamed N, Mohamed KG, Ahmed A. In Vitro and In Vivo evaluation of cubosomes containing 5-Fluorouracil for liver targeting. Acta Pharm. Sin. B. 2015; 5(1): 79-88. https://doi.org/10.1016%2Fj.apsb.2014.12.001.
  • [30] Hanan ME, Alia B, Nevine SA, Nihal ES. Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine. Chem. Pharm. Bull. 2018; 66(12): 1165-1173. https://doi.org/10.1248/cpb.c18-00615.
  • [31] Alaa EE, Salwa S, Mahmoud G. Formulation and evaluation of cubosomes drug delivery system for treatment of Glaucoma: Ex vivo permeation and in vivo pharmacodynamic study. J. Drug Deliv. Sci. Technol. 2019; 52. http://dx.doi.org/10.1016/j.jddst.2019.04.036.
  • [32] Hoda ET, Islam AK, Heba MS. Novel cubosome based system for ocular delivery of Acetazolamide. Drug Deliv. 2021; 1: 2177-2186. https://doi.org/10.1080%2F10717544.2021.1989090.
  • [33] Muheem A, Shakeel F, Warsi M, Jain G, Ahmad F. A Combinatorial Statistical Design Approach to Optimize the Nanostructured Cubosomal Carrier System for Oral Delivery of Ubidecarenone for Management of Doxorubicin-Induced Cardiotoxicity. J. Pharm. Sci. 2017; 106(10): 1-17. https://doi.org/10.1016/j.xphs.2017.05.026.
  • [34] Hosny KM. Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation. Int. J. Nanomedicine. 2020; 15: 5113-5129. https://doi.org/10.2147/IJN.S261855.
  • [35] Ankit A, Prakash G, Vinay CH. Determination of Mucoadhesive behaviour of Timolol maleate liquid crystalline cubogel by different Techniques. Asian J. Pharm. Res. 2019; 9(1): 7-11. https://doi.org/10.5958/2231-5691.2019.00002.9.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Rajani Thoutreddy 0000-0003-4059-6040

Koteswara Rao Gsn 0000-0003-1257-7133

Narender Malothu 0000-0002-3069-5742

Chakravarthi Guntupalli 0000-0003-3777-3157

Pavani Sriram 0000-0002-4484-2117

Rajasekhar Reddy Alavala 0000-0002-2610-8111

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 5

Kaynak Göster

APA Thoutreddy, R., Gsn, K. R., Malothu, N., Guntupalli, C., vd. (2025). Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD. Journal of Research in Pharmacy, 27(5), 2067-2078.
AMA Thoutreddy R, Gsn KR, Malothu N, Guntupalli C, Sriram P, Alavala RR. Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD. J. Res. Pharm. Temmuz 2025;27(5):2067-2078.
Chicago Thoutreddy, Rajani, Koteswara Rao Gsn, Narender Malothu, Chakravarthi Guntupalli, Pavani Sriram, ve Rajasekhar Reddy Alavala. “Development and Evaluation of Lidocaine Hydrochloride Cubosomes Directed by QbD”. Journal of Research in Pharmacy 27, sy. 5 (Temmuz 2025): 2067-78.
EndNote Thoutreddy R, Gsn KR, Malothu N, Guntupalli C, Sriram P, Alavala RR (01 Temmuz 2025) Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD. Journal of Research in Pharmacy 27 5 2067–2078.
IEEE R. Thoutreddy, K. R. Gsn, N. Malothu, C. Guntupalli, P. Sriram, ve R. R. Alavala, “Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD”, J. Res. Pharm., c. 27, sy. 5, ss. 2067–2078, 2025.
ISNAD Thoutreddy, Rajani vd. “Development and Evaluation of Lidocaine Hydrochloride Cubosomes Directed by QbD”. Journal of Research in Pharmacy 27/5 (Temmuz 2025), 2067-2078.
JAMA Thoutreddy R, Gsn KR, Malothu N, Guntupalli C, Sriram P, Alavala RR. Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD. J. Res. Pharm. 2025;27:2067–2078.
MLA Thoutreddy, Rajani vd. “Development and Evaluation of Lidocaine Hydrochloride Cubosomes Directed by QbD”. Journal of Research in Pharmacy, c. 27, sy. 5, 2025, ss. 2067-78.
Vancouver Thoutreddy R, Gsn KR, Malothu N, Guntupalli C, Sriram P, Alavala RR. Development and Evaluation of Lidocaine Hydrochloride Cubosomes directed by QbD. J. Res. Pharm. 2025;27(5):2067-78.