Lipid Horizons: Recent Advances and Future Prospects in LBDDS for Oral Administration of Antihypertensive Agents

Table 5

Various LBDDSs of antihypertensive compounds.

S. no.	Drug candidate	BCS class	Absorbent/polymers/bioenhancer/other excipients	Lipid/oils	Surfactant	Cosurfactant/other excipients	Formulation approach	Year of publication	Reference no.	Outcomes
Calcium channel blockers
1	Amlodipine	Class I		Oleic acid	Tween 80	Transcutol P	NE	2009	[154]	This study signifies that nanoemulsion serves as a potential vehicle for improving the transdermal delivery of amlodipine
2	Amlodipine basilate	Class 1	—	Labrafil M	Tween 80	Ethanol	NE	2011	[155]	This study was indicating 3-fold increase in the whole residence time of NE that is suggested NE as drug carriers for improving the bioavailability in comparison of marketed formulation
3	Felodipine	Class II	Aerosil 200	Acconon E	Cremophor EL	Lutrol E300	SNEDDS	2013	[20]	Felodipine containing SNEDDS and S-SNEDDS has significant potential to improve its absorption through git and may serve a capable delivery via oral administration
4	Isradipine	Class II		Vitamin E TPGS	Sodium lauryl sulfate		Nanosuspension	2012	[156]	In vitro dissolution study showed that the dissolution rate of nanosuspensions (98.60%) and saturation solubility (98.76 μg/ml) compared with the coarse drug (11.53% and 14.1 μg/ml, respectively) had been significantly enhancing and pharmacokinetic study showed increases in AUC0–48 by 2.0-fold and increases the and in comparison to pure drug suspension
5	Isradipine	Class II	Neusilin us2	Labrafil® M2125	Capmul® MCM L8	Cremophor® EL	S-SEDDS	2014	[22]	The results of this study showed that in vitro drug release rate was increased about 18-fold and in vivo bioavailability was increased about 2.5-fold from marketed formulation
6	Isradipine	Class II	—	Trimyristin and tristerin	Poloxamer 188		SLN	2014	[20]	The drug release from SLNs formulation is found to be around 99% within 12 hours
7	Isradipine	Class II	—	Steric acid, glyceryl monostearate	—	—	SLN	2016	[157]	This study included SLN prepared with two lipids in different concentrations. The pharmacodynamics studies of optimized formulation showed reduction in BP upto 36 hrs and confirmed the suitable carrier for oral administration
8	Isradipine	Class II	—	Glyceryl monostearate: soya lecithin	—	Eudragit L100, rutin	SLN	2018	[158]	Pharmacokinetic study shows the 3.2–4.7-fold increase in the bioavailability of coated SLN of isradipine as compared to conventional drug suspension. In vivo studies show greater absorption orally
9	Isradipine	Class II	—	Tricetin	Tween 20	Transcutol	NE	2020	[159]	This study showed greater dissolution profile and solubility of isradipine
10	Lercanidipine	Class II	Neusilin	Capmul MCM L8	Tween 80	PEG 400	S-SEDDS	2012	[160]	Optimized S-SEDDS showed the greater dissolution rate as compared to pure drugs and proved that SEDDS formulations are alternative approaches for oral route administration
11	Lercardipine HCL	Class II	Avicel PH 101	Peppermint oil	Propylene glycol	PEG 400	S-SEDDS	2020	[24]	Optimized formulation showed enhanced solubility and dissolution profile of the lercardipine hydrochloride in comparison with pure drug
										The S-SEDDS had shown good stability
12	Nifedipine	Class II	—	Cremophor®E L (polyoxyl 35 castor oil)	Caprylic/capric glyceride	Transcutol® HP (diethylene glycolmonoethy l ether)	SNEDDS	2014	[161]	Optimized formulation shows significant increase in the AUC 0–12 h and 2.9 folds in comparison to pure drug powder and the AUC0–12 h of nifedidine loaded SNEDDS and drug powder was 4082.6 ± 621.7 and 1413.4 ± 388.4 ng/mL·h, respectively
13	Nifedipine	Class II	Aerosil® 200	Imwitor® 742	Cremophor (®) RH40	Span (®) 80	SNEDDS	2014	[162]	It is concluded that nifedipine loaded SNEDDS is favorable dosage form with good in vitro studies
14	Nimodipine	Class II	—	Glucire 44/14	Transcutol p	Plurol oleique CC 497	SEDDS	2008	[163]	SEDDS formulation shows significant improvement in the in vitro and in vivo performance, i.e., it is a novel effective alternative for the development of nimodipine formulation
15	Nimodipine	Class II	—	Peppermint oil	Cremphor EL	PEG 400	SEDDS	2018	[164]	Study successfully discriminated the influence of design variables on %age of the nimodipine in aqueous which signifies the segment of SEDDS arranged for instant absorption
16	Nimodipine	Class II	—	Peceol	Transcutol P	PEG 400	SNEDDS	2019	[165]	Optimized SNEDDS formulation of nimodipine shows improved in vitro dissolutions and absorption profile of the drugs and also indicate that the stability of drug in formulation is good
17	Nitrendipine	Class II	—	Tripalmitin/glyceryl monostearate/cetyl palmitate	Soy phosphatidylcholine 95%	Poloxamer 188	SLN	2006	[166]	Bioavailability of lipophilic drugs like nitrendipine could be improved by suitably incorporating into nimodipine SLN and enhancing the bioavailability of the drugs from 3.21 to 5.35 folds on i.d. administration
18	Nitrendipine	Class II	Carbopol	Trimyristin	Tween 80	—	SLN and NLC hydrogels	2008	[167]	These transdermal gels show abundant efficacy and a feasible option of effective and controlled management of high blood pressure
19	Nitrendipine	Class II	—	Caproyl 90®	Tween 80	Transcutol P®/solutol HS-15®	Intranasal NE	2009	[168]	In vivo absorption studies show improved absorption and an instant onset of action and relative bioavailability of 60.44%, that is greater than the marketed tablets and pure suspension
20	Niterndipine	Class II	—	Capmul MCM: triacetin	Kolliphor ELP	Transcutol HP	NE gel	2020	[169]	This gel improves the poor penetration and it could be used as a potential carrier for the delivery of nitrendipine
ACE inhibitors
21	Captopril	Class I	Curcumin	Glyceryl monooleate	Tween 20	PEG 400	NE	2015	[170]	This study shows that curcumin synergism effect on captopril activity and NE formulation increase the poor solubility of the drug
22	Captopril	Class I	—	Castor oil	Kolliphor RH40: Kolliphor EL	Glycerol	SEDDS	2020	[171]	This study provides indication for a sustained release from SEDDS formulation of captopril drug
23	Ramipril	Class II	—	Safsol 218	Tween 80	Carbitol 18	NE	2007	[172]	This study revealed that optimized formulation of ramipril NE could be used for geriatric and pediatric patients in liquid unit dosage form. In vitro release was highly significant as compared with pure suspension and marketed formulation
24	Ramipril	Class II	—	Safsol 218	Cremophor EL	Carbitol	NE	2008	[173]	Bioavailability of ramipril is increased 4.29-fold to drug suspension and 1.76-fold increase that of marketed tablet. Degradation rate was slow in NE with aqueous phase (buffered solution pH-5.0) in comparison to other formulation, i.e., these results indicated improved stability of ramipril in NE
25	Ramipril	Class II	—	Glyceryl monooleate	Span 20	—	SLN	2011	[174]	The optimized formulation shows the prolonged drug release as compared to other formulations with different lipids and surfactants
26	Ramipril	Class II	—	Capmul PG8 NF	Gelucire 44/14	Transcutol P	SNEDDS	2016	[175]	Optimized NE formulation shows significant improved stability, solubility, and dissolution rate of the ramipril
27	Ramipril	Class II	Syloid	Capmul MCM/Polyoxyethylene hydrogenated castor oil	—	Transcutol P	S-SNEDDS	2019	[176]	Results of this studies show significant improvement in solubility and stability against heat, moisture, and mechanical stress during manufacturing and storage
AT II receptor blockers
28	Candesartan cilexetil	Class II	—	Miglyol 812	Labrasol	Tween 80/Cremophor EL	SMEDDS	2010	[177]	The optimized formulation shows the higher drug release rate than the marketed formulation; this study indicates the SMEDDS had a potential to enhance the solubility and dissolution rate of the poorly soluble drug compound
29	Candesartan cilexetil	Class II	—	Lauroglycol 90	Tween 40	Transcutol P	SNEDDS	2015	[178]	This study shows significant improvement, permeability, and oral bioavailability of the drugs from the SNEDDS formulation
30	Candesartan cilexetil	Class II	—	Peppermint oil	Cremophor RH40	Labrasol	SNEDDS	2019	[179]	In this study, SNEDDS formulation of drugs shows rapid onset of action and prolonged therapeutic activity
										SNEDDS improved the oral bioavailability of candesartan about 1.69-fold as compared with the marketed formulation
31	Candesartan cilexetil	Class II	Aerosil and Avicel 101	Cinnamon oil	Tween 80: polaxomer 407	Transcutol P	S-SNEDDS	2017	[180]	This study concluded that S-SNEDDS is a favorable approach to enhance the wettability, poor solubility, dissolution rate, and stability of candesartan cilexetil
32	Candesartan cilexetil	Class II	—	Capryol 90®	Tween 80	Transcutol P	SNEDDS	2019	[181]	The optimized formulation of SNEDDS shows promising delivery system with rapid onset of action and prolonged therapeutic effect of drugs
33	Candesartan	Class II	—	Capryol 90®	Captex 500	Labrasol	SNEDDS	2018	[182]	This study shows the higher drug release from the formulation into the blood stream as compared to marketed formulation and pure suspension
34	Candesartan cilexetil	Class II	—	Triacetin oil	Cremophore RH 40	Transcutol P	SNEDDS	2020	[183]	These studies indicate the increased dissolution profile of candesartan cilexitil (98%) in comparison to pure drug suspension (45%)
35	Candesartan cilexetil	Class II	—	Soybean oil	Solutol HS-15	Tween 80	NE	2011	[184]	The results of this studies show that NEs are very effective formulation approach for improving the oral absorption of insoluble drug candidate. 8 candesartan enhanced 10 folds results when incorporated into the NE
36	Candesartan cilexetil	Class II	—	Soybean lecithin: glycerol monostearate	Tween 80	—	SLN	2012	[185]	The pharmacokinetic studies show improvement in oral bioavailability over 12-fold after encapsulation into SLN
37	Candesartan cilexetil	Class II	Dynasan 116	Egg-lecithin (E-80)	Poloxamer-188	—	SLN	2014	[186]	These studies conclude that optimized SLN of drug showed 2.75-fold enhancement in the oral bioavailability and confirmed SLN is suitable for carrying candesartan cilexitil for oral route administration
38	Candesartan cilexetil	Class II	Hydroxypropyl methylcellulose	Pluronic® F 127		—	Nanocrystals	2016	[187]	This study investigated that nanocrystals are suitable for improvement of the oral bioavailability of the candesartan cilexitil
39	Candesartan cilexetil	Class II	—	Pluronic P85	Span 60	—	Niosomes	2014	[188]	This study concluded that niosomes increase the solubility and stability of drugs against the bile distruption and had an great potential to increase the oral bioavailability of poorly water-soluble drug candidates via encapsulation in lipid carrier
40	Candesartan cilexetil	Class II	Maltodextrin/diacetyl phosphate	Cholesterol/	Span 60	—	Proniosomes	2016	[189]	These studies indicate proniosomes of candesartan a promising formulation for the enhancement of oral bioavailability and patient compliance
41	Candesartan cilexetil	Class II	Chitosan	Peceol™	Span 60	—	Niosomes	2021	[190]	These studies conclude that chitosan coated or uncoated niosomes of candesartan cilexitil shows better oral absolute bioavailability
42	Olmesartan midoxomil	Class II	—	Capryol 90	Tween 20	Tetraglycol	SMEDDS	2009	[191]	This study shows that SMEDDS increases the relative oral bioavailability about 170% as compared to that pure drug suspension. SMEDDS increased the solubility and permeability by inhibiting the efflux pump
43	Olmesartan midoxomil	Class II	—	Capryol 90	Labrasol	Transcutol	SMEDDS	2011	[192]	This study concluded that SMEDDS enhances the oral bioavailability of olmesartan medoxomil in vivo 2.7-fold as compared to pure drug suspension
44	Olmesartan midoxomil	Class II	—	Acrysol EL 135	Tween 80	Transcutol P	SMEDDS	2013	[193]	This study concluded in vivo and ex vivo diffusion rates from SMEDDS and is greater than the pure drug suspension of the olmesartan medoxomil. So, it is a promising delivery system for improving the oral bioavailability of poorly water-soluble drug candidates
45	Olmesartan midoxomil	Class II	—	Oleic acid	Tween 80	Transcutol	SMEDDS	2019	[194]	This study showed SMEDDS increased the solubility and bioavailability of hydrophobic olmesartan medoxomil while reducing the side effects of drug such as enteropathy
46	Olmesartan midoxomil	Class II	—	Soyabean oil 700	Sefsol 218	Solutol HS-15	NE	2014	[75]	The pharmacokinetic studies showed increased AUC about 2.8 folds and sustained release upon oral administration
47	Olmesartan midoxomil	Class II	Aerosil 200	Capryol 90	Cremophor RH40	Transcutol HP	S-SNEDDS	2016	[76]	This study concluded that in vitro dissolution rate of olmesartan is increased, and pharmacokinetic behavior of drug is also improved as compared to the pure drug suspension
48	Olmesartan midoxomil	Class II	Silicon dioxide	Capmul MCM®	Tween 80®	PEG 400	S-SEDDS	2012	[195]	This study concluded that S-SEDDS had a better handling potential as compared with NE and in vitro release was similar
49	Telmisartan	Class II	—	Acrysol® EL 135	Tween® 20	Carbitol®	SNEDDS	2011	[196]	The in vivo study shows 7.5-fold enhancement of the oral bioavailability of telmisartan from SNEDDS as compared to the pure drug suspension
50	Telmisartan	Class II	Neusilin US2	Oleic acid	Tween 80	PEG 400	S-SMEDDS	2012	[197]	This study concluded that telmisartan-loaded S-SMEDDS shows improvement in dissolution profile of the drug as compared with pure drug suspension
51	Telmisartan	Class II	Micro-crystalline cellulose	Castor oil	Tween 20	Propylene glycol	S-SMEDDS	2014	[198]	This study concludes that in vitro release of telmisartan from S-SMEDDS was 100% in about 120 min, that was higher than the pure drug suspension
52	Telmisartan	Class II	—	Capmul MCM®	Tween 80	Propylene glycol	SMEDDS	2015	[199]	The result concluded that the pharmacokinetic study shows 1.54-fold increase in bioavailability of telmisartan-loaded SMEDDS in comparison with pure drug and marketed formulation
53	Telmisartan	Class II	—	Labrafil 1944	Kolliphor ELP: span 80	PEG 400: Ethanol	SNEDDS	2017	[200]	This study concluded that telmisartan-loaded SNEDDS could increase the oral bioavailability as compared to pure drug suspension
54	Telmisartan	Class II	Phospholipid	Capryol 90	Tween 80	Tetraglycol	SMEDDS	2018	[201]	The optimized formulation shows pH independent high dissolution of temisdartan. So, this study suggested that the phospholipid complex with SMEDDS is beneficial for enhancement of the dissolution of hydrophobic drug
55	Telmisartan	Class II	—	Cinnamon	Gelucire 44/14	Transcutol	SMEDDS	2018	[202]	The results of the study concluded that in vivo studies of telmisartan-loaded SMEDDS had successfully increased the and AUC of the drug as compared to pure drug suspension
56	Telmisartan	Class II	—	Capmul MCM EP	Labrasol	Transcutol HP		2019	[203]	The developed and optimized formulation of telmisartan-loaded SMEDDS shows significant improvement in the dissolution rate and profile in comparison to pure drug suspension. This research shows that SMEDDS has a great potential for delivering the BCS-II class drugs
57	Telmisartan	Class II	—	Capmul® MCM	Cremophor® RH40	Tetraglycol	Su-SEDDS	2020	[204]	The in vivo pharmacokinetic study shows that oral bioavailability of drug from Su-SEDDS was about 1.2-fold greater than the pure drug suspension
58	Telmisartan	Class II	—	Capmul PG 8	Cremophor RH 40	Transcutol P	S-SMEDDS	2021	[205]	This study shows that the in vitro dissolution test is significantly higher than the plain telmisartan
59	Telmisartan	Class II	Carbopol 934	Labrafil®M 2125 CS	Acrysol®EL 135	Carbitol®	NE gel	2015	[206]	The study concluded that optimized formulation of NE gel showed higher bioavailability as compared to conventional gel and it showed greater permeation and penetration rate in in vivo and in vitro
60	Telmisartan	Class II	—	Oleic acid	Tween 80	PEG	NE	2017	[207]	Optimized formulation showed greater stability and drug release in comparison with conventional formulation and showed enhanced bioavailability
61	Telmisartan	Class II	Chitosan	Sefsol 218 and oleic acid	Tween 20	Transcutol P	Mucoadhesive nanoemulgel	2021	[208]	This study concluded that the telmisartan mucoadhesive nanoemulgel, coated with chitosan, emerged as a promising technique for the treatment of tuberculosis, facilitating direct nose-to-brain delivery based on in vivo and ex vivo results
62	Telmisartan	Class II	—	Soya PL phospholipids	Brij 35	—	Proniosomes	2020	[209]	The optimized formulation in vivo study showed Cmax enhances 1.5-fold and AUC increases about 3-fold and also produces sustained effect when it is compared with the marketed tablets
63	Telmisartan	Class II	—	Cholesterol	Span 60	—	Niosomes	2021	[210]	This study concluded that telmisartan encapsulated niosomes had shown better drug release when compared with pure drug
64	Telmisartan	Class II	—	Soya lecithin	Span 80	Tween 80	Transferosomes	2018	[211]	The results of the optimized formulation showed better entrapment efficacy (50.72%), zeta potential (27.6 mv%), and drug diffusion (−58 ± 2.4%) for effective control of cardiovascular disorders
65	Losartan potassium	Class II	Egg-lecithin	Cholesterol	Span 60	—	Proniosomes	2009	[212]	The results of in vivo pharmacokinetic study showed significant increase in the bioavailability about 1.93-fold as compared with oral formulation of losartan potassium
66	Valsartan	Class II	—	Capmul MCM	Tween 80	PEG 400	SMEDDS	2010	[213]	Results of the study showed higher drug release and bioavailability of valsartan from SMEDDS
67	Valsartan	Class II	—	Castor oil	Tween 80	PEG 600	SEDDS	2011	[214]	The optimized formulation shows adequate improvement in the drug release and stability of the drug from valsartan loaded SEDDS
68	Valsartan	Class II	—	Labrasol	Tween 20	PEG 400	SNEDDS	2012	[215]	The optimized formulation showed significantly enhanced solubility and stability of the valsartan loaded in SNEDDS as compared with marketed formulation. This improvement in the solubility could lead to higher drug oral bioavailability
69	Valsartan	Class II	Neusilin US2	Capmul MCM	Kolliphor HS-15	PEG 400	S-SEDDS	2015	[216]	The results of the study showed increase in the bioavailability of valsartan from S-SEDDs about 1.6 folds as compared with plain drug
70	Valsartan	Class II	Florite® PS-10 and Vivapur® 105	Capmul MCM	Tween 80	Transcutol® P and poloxamer 407	S-SuSMEDDS	2017	[217]	The pharmacokinetic study concluded in rats the relative bioavailability of the S-SuSMEDDS granules and DIOVAN powder was about 107% and 222%, respectively. Therefore, this technique has a great potential for developing solid dosage form of liquefied formulation for improving oral bioavailability of hydrophobic drugs
71	Valsartan	Class II	—	Capmul® MCM	Tween® 20	Transcutol® P	SuSMEDDS	2017	[218]	Results showed excellent in vivo and in vitro bioavailability of the drug from optimized formulation
72	Valsartan	Class II	L-HPC and Florite® PS-10	Capmul MCM	Tween 80	Gelucire® 44/14	S-SuSMED	2019	[219]	The study concluded that optimized S-SuSMED tablets enhanced the oral bioavailability in rat about 177–198% as compared with plain valsartan and DIOVAN
73	Valsartan	Class II	—	Phospholipon 90G	Sodium deoxycholate		Nanotransferosomes	2012	[220]	The in vivo study on Wistar rats showed that nanotransferosomes enhance the transdermal delivery of valsartan drug and produces the prolonged control on blood pressure up to 48 hrs
74	Valsartan	Class II	—	Phospholipon 90G	Span 40	—	Transferosomes	2020	[221]	This study concluded that valsartan-loaded transferosomes patch will be effective in reducing the frequency of dosing, as it has produced sustained effects and enhanced patient compliance
75	Valsartan	Class II	—	Cholesterol	Span 60	—	Niosomes	2019	[222]	The results of this study showed controlled release about 24 hrs (98.55) of the valsartan from the niosomes
76	Valsartan	Class II	Lecithin	Cholesterol	Span 60	—	Proniosomes	2011	[223]	The study concluded that proniosomes prepared with span 60, cholesterol, and lecithin have an high encapsulation efficacy, release rate, and stability as compared with formulation composition
Beta-blockers
77	Atenolol/metaprolol/danazol	Class III,/II/I	—	Lauroglycol ® 90	Pluronic® P104	Pluronic® L62 or L81	Nanoemulsion	2007	[150]	The study concluded that BCS-1 and II drugs show higher permeability as compared with plain drugs. Atenolol increases 2.5 folds, danazol increases 3.2 folds, and metoprolol increases 1.4 folds
78	Carvedilol	Class II	—	Labrafil M 1944CS	Tween 80	Transcutol P	SMEDDS	2005	[224]	The results of the study showed that increase in vitro dissolution rate of the carvedilol from SEDDS and SMEDDS about 2 folds than marketed tablets
79	Carvedilol	Class II	—	Gelucire 44/14	Lutrol F68	Transcutol P	Self-emulsifying osmotic pump	2007	[225]	The results of the studies show that drug release from self-emulsifying osmotic pump was controlled and follows zero-order kinetic and improved the oral bioavailability
80	Carvedilol	Class II	—	Capmul PG8	Cremophor EL	Transcutol HP	SNEDDS	2011	[226]	This study shows accelerated stability of the optimized formulation for 6 months. In situ perfusion study on Wistar rats showed improved permeability and absorption potential about several folds in comparison to marketed formulation
81	Carvedilol	Class II	—	Capmul MCM	Nikkol HCO 50	—	SNEDDS	2012	[227]	The results of the studies were stable during the 6 months of study periods. And optimized formulation had a potential of enhancement of oral bioavailability of carvedilol
82	Carvedilol	Class II	Hydroxypropyl methylcellulose/polaxomer	Oleic acid	Labrafil	Labrafac PG	SEDDS	2014	[228]	This study concluded that carvedilol loaded SEDDS showed drug permeability through the rat intestine was about 2.76 folds greater than the control
83	Carvedilol	Class II	—	Caproyl 90	Tween 20	Transcutol HP	SEDDS	2017	[229]	The results of this study concluded that optimized formulation of carvedilol loaded SEDDS expressed rapid onset of action and improved the antihypertensive activity
84	Carvedilol	Class II	—	Cremophor RH40	PEG 400	HPMC-E5	Su-SEDDS	2020	[230]	The in vivo results of the study showed increase in the permeability and bioavailability about 2.2 folds and 3.2 folds, respectively
85	Carvedilol	Class II	—	Castor oil	Solutol or Kolliphor RH40	Solutol or Kolliphor RH40	L-SEDDS	2021	[231]	The study concluded increase in the in vitro dissolution and stability of the drug as compared with the plain drug
86	Carvedilol	Class II	Aerosil	Peceol™	Tween® 80	Labrasol®	S-SNEDDS	2021	[232]	The results of the study showed that increases in the solubility, dissolution rate, and oral bioavailability were about 6.1 folds, 1.8 folds, and 1.4 folds, respectively, of the carvedilol from S-SEDDS formulation
87	Carvedilol	Class II	—	Oleic acid/isopropyl myristate	Tween 80	Transcutol P	Transdermal NE	2008	[233]	The results of the study concluded that there were increases in solubility of the drug in 4500 folds, decrease in the activation energy about 88% during thermodynamic studies, and the optimized formulation was nonirritant for the skin suggested by irritation studies
88	Carvedilol	Class II	—	Steric acid	Polaxomer 188	Sodium taurocholate and ethanol	SLN	2009	[234]	The results of the study showed decrease in the bioavailability of carvedilol on increasing the concentration of polaxomer 188 in formulations about 4.91–2.84 folds after intraduonal administration in Wistar rats
89	Carvedilol	Class II	Neusilin US2	Stearic acid	—	Dichloromethane and methanol	SLN	2010	[235]	This study concluded that SLN increases the efficacy, release rate, and stability of the drug in comparison to plain nanosuspension
90	Carvedilol	Class II	N-Carboxymethyl chitosan	Monoglyceride	Soya lecithin and poloxamer 188	—	SLN	2012	[236]	In vivo study rats showed SLN coated with n-carboxymethyl chitosan increases the bioavailability of carvedilol in comparison to uncoated after oral administration
91	Carvedilol	Class II	—	Compritol or Precirol	Poloxamer 188	Lecithin	Intranasal SLN	2016	[237]	The in vivo pharmacokinetic study showed increases in absolute bioavailability (350.63%) in comparison to oral carvedilol formulation (24.11%)
92	Carvedilol	Class II	—	Phospholipon 100 H and cholesterol	Ethanol	Transcutol HP	Transdermal ethosomal gel	2019	[238]	The study concluded by ethosomes having a great potential to increase the skin penetration with extended carvedilol antihypertensive action
93	Carvedilol	Class II	—	Lipid	Ethanol	Propylene glycol	Transdermal ethosomes	2021	[239]	In vitro studies of drug release showed sustained release of the drug from ethosomes and ethosomal gel and enhanced the penetration via skin
94	Propranolol hydrochloride	Class I	—	Lecithin	Sorbitol	—	Proliposomes	1995	[240]	This study concluded that proliposome had a great potential for the sustained effect when applied to mucosal membrane
95	Propranolol hydrochloride	Class I	—	Cholesterol	Phosphatidyl ethanolamine	—	Liposomal gel	2015	[241]	In vivo study showed increases in the propranolol hydrochloride concentration in skin about 74 folds as compared to plain drug

BCS, Biopharmaceutical Classification System; SEDDS, self-emulsifying drug delivery system; SNEDDS, self-nanoemulsifying drug delivery system. SMEDDS, self-microemulsifying drug delivery system; S-SEDDS, solid self-emulsifying drug delivery system; SLN, solid lipid particles; NLC, nanostructured lipid carriers; PEG, polyetylene glycol;. NE, nanoemulsion.